BioMedLib Search Engine [ goto HOMEPAGE ]

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Dual positive and negative regulation of wingless signaling by adenomatous polyposis coli.

The majority of colorectal carcinomas contain truncating mutations in the adenomatous polyposis coli (APC) tumor suppressor, a negative regulator of Wnt/Wingless signaling.

Here, we demonstrate that Drosophila Apc homologs also have an activating role in both physiological and ectopic Wingless signaling.

The Apc amino terminus is important for its activating function, whereas the beta-catenin binding sites are dispensable.

Apc likely promotes Wingless transduction through down-regulation of Axin, a negative regulator of Wingless signaling.

Given the evolutionary conservation of APC in Wnt signal transduction, an activating role may also be present in vertebrates with relevance to development and cancer.

Faculty of 1000. commentaries/discussion - See the articles recommended by F1000Prime's Faculty of more than 8,000 leading experts in Biology and Medicine. (subscription/membership/fee required).

FlyBase. FlyBase .

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 18202290.001).

[ISSN] 1095-9203

[Journal-full-title] Science (New York, N.Y.)

[ISO-abbreviation] Science

[Language] ENG

[Grant] United States / NCI NIH HHS / CA / R01 CA105038; United States / NCI NIH HHS / CA / KO8CA078532; United States / NCI NIH HHS / CA / R01CA105038

[Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.

[Publication-country] United States

[Chemical-registry-number] 0 / APC protein, Drosophila; 0 / APC1 (adenomatous polyposis coli) protein, Drosophila; 0 / APC2 protein, Drosophila; 0 / Adaptor Proteins, Signal Transducing; 0 / Armadillo Domain Proteins; 0 / Axin Protein; 0 / Cytoskeletal Proteins; 0 / Drosophila Proteins; 0 / Proto-Oncogene Proteins; 0 / Transcription Factors; 0 / Tumor Suppressor Proteins; 0 / Wnt1 Protein; 0 / armadillo protein, Drosophila; 0 / axin protein, Drosophila; 0 / wg protein, Drosophila

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Polymorphisms in the adenomatous polyposis coli (APC) gene and advanced colorectal adenoma risk.

While germline mutations in the adenomatous polyposis coli (APC) gene cause the hereditary colon cancer syndrome (familial adenomatous polyposis (FAP)), the role of common germline APC variants in sporadic adenomatous polyposis remains unclear.

We studied the association of eight APC single nucleotide polymorphisms (SNPs), possibly associated with functional consequences, and previously identified gene-environment (dietary fat intake and hormone replacement therapy (HRT) use) interactions, in relation to advanced colorectal adenoma in 758 cases and 767 sex- and race-matched controls, randomly selected from the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Cases had at least one verified advanced adenoma of the distal colon; controls, a negative sigmoidoscopy.

We did not observe an association between genotypes for any of the eight APC SNPs and advanced distal adenoma risk (P(global gene-based)=0.92).

Frequencies of identified common haplotypes did not differ between cases and controls (P(global haplotype test)=0.97).

However, the risk for advanced distal adenoma was threefold higher for one rare haplotype (cases: 2.7%; controls: 1.6%) (odds ratio (OR)=3.27; 95% confidence interval (CI)=1.08-9.88).

The genetic association between D1822V and advanced distal adenoma was confined to persons consuming a high-fat diet (P(interaction)=0.03).

Similar interactions were not observed with HRT use.

In our large, nested case-control study of advanced distal adenoma and clinically verified adenoma-free controls, we observed no association between specific APC SNPs and advanced adenoma.

Fat intake modified the APC D1822V-adenoma association, but further studies are warranted.

[MeSH-major] Adenomatous Polyposis Coli / genetics. Genes, APC. Germ-Line Mutation / genetics. Polymorphism, Single Nucleotide / genetics

Genetic Alliance. consumer health - Familial Adenomatous Polyposis (FAP).

[Email] Email this result item

Email the results to the following email address:   [X] Close

[Copyright] Copyright 2010 Elsevier Ltd. All rights reserved.

[Cites] Cancer Res. 2008 Jan 15;68(2):358-63 [18199528.001]

[Cites] Genomics. 1996 Jun 1;34(2):268-70 [8661068.001]

[Cites] N Engl J Med. 2000 Jul 20;343(3):169-74 [10900275.001]

[Cites] BMJ. 2000 Oct 7;321(7265):886-9 [11021873.001]

[Cites] Control Clin Trials. 2000 Dec;21(6 Suppl):251S-272S [11189683.001]

[Cites] Control Clin Trials. 2000 Dec;21(6 Suppl):349S-355S [11189687.001]

[Cites] Cancer Res. 2001 Feb 1;61(3):1000-4 [11221825.001]

[Cites] Eur J Cancer. 2001 Mar;37(4):499-502 [11267860.001]

[Cites] Genet Test. 2001 Summer;5(2):141-6 [11551102.001]

[Cites] J Med Screen. 2001;8(3):137-44 [11678553.001]

[Cites] J Natl Cancer Inst. 2001 Dec 5;93(23):1799-805 [11734596.001]

[Cites] Eur J Cancer. 2010 Mar;46(4):765-81 [20116997.001]

[Cites] Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2225-8 [10681434.001]

[Cites] Cancer Lett. 2000 Feb 28;149(1-2):203-6 [10737725.001]

[Cites] N Engl J Med. 2000 Jul 20;343(3):162-8 [10900274.001]

[Cites] J Natl Cancer Inst. 2004 Jun 16;96(12):921-5 [15199111.001]

[Cites] Int J Cancer. 2004 Oct 20;112(1):161-3 [15305389.001]

[Cites] Nat Rev Cancer. 2004 Oct;4(10):769-80 [15510158.001]

[Cites] IARC Sci Publ. 1980;(32):5-338 [7216345.001]

[Cites] Nature. 1987 Aug 13-19;328(6131):614-6 [3039373.001]

[Cites] Genetics. 1988 Nov;120(3):849-52 [3224810.001]

[Cites] Anticancer Res. 1990 Sep-Oct;10(5A):1189-200 [2241098.001]

[Cites] Cell. 1991 Aug 9;66(3):589-600 [1651174.001]

[Cites] Science. 1991 Aug 9;253(5020):661-5 [1651562.001]

[Cites] J Natl Cancer Inst. 1992 Jan 15;84(2):91-8 [1310511.001]

[Cites] N Engl J Med. 1992 Mar 5;326(10):658-62 [1736104.001]

[Cites] J Natl Cancer Inst. 1993 Jun 2;85(11):884-91 [8388061.001]

[Cites] Hum Mol Genet. 1992 Jul;1(4):229-33 [1338904.001]

[Cites] Nucleic Acids Res. 1996 Jan 1;24(1):121-4 [8594558.001]

[Cites] Gastroenterology. 1996 Apr;110(4):1028-30 [8612989.001]

[Cites] Am J Hum Genet. 2002 Feb;70(2):425-34 [11791212.001]

[Cites] Cancer Epidemiol Biomarkers Prev. 2002 Jul;11(7):622-9 [12101109.001]

[Cites] Genet Epidemiol. 2002 Oct;23(3):221-33 [12384975.001]

[Cites] Am J Hum Genet. 2002 Nov;71(5):1227-34 [12384857.001]

[Cites] Cell. 2002 Oct 18;111(2):241-50 [12408868.001]

[Cites] Cancer Epidemiol Biomarkers Prev. 2003 Oct;12(10):1023-8 [14578138.001]

[Cites] Int J Cancer. 2004 Jan 10;108(2):287-92 [14639617.001]

[Cites] J Natl Cancer Inst. 2003 Dec 3;95(23):1765-71 [14652238.001]

[Cites] Hum Mol Genet. 1997 Feb;6(2):285-9 [9063749.001]

[Cites] Nat Genet. 1997 Sep;17(1):79-83 [9288102.001]

[Cites] Ann Intern Med. 1998 May 1;128(9):705-12 [9556463.001]

[Cites] Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10722-7 [9724771.001]

[Cites] Nat Genet. 1998 Sep;20(1):62-5 [9731533.001]

[Cites] Gastroenterology. 1999 Jan;116(1):58-63 [9869603.001]

[Cites] J Natl Cancer Inst. 1999 Jun 2;91(11):916-32 [10359544.001]

[Cites] Scand J Gastroenterol. 1999 Apr;34(4):414-20 [10365903.001]

[Cites] Int J Cancer. 2005 Jan 1;113(1):126-32 [15386431.001]

[Cites] Bioinformatics. 2005 Jan 15;21(2):263-5 [15297300.001]

[Cites] Breast Cancer Res. 2005;7(2):R171-5 [15743496.001]

[Cites] CA Cancer J Clin. 2005 Mar-Apr;55(2):74-108 [15761078.001]

[Cites] Cancer Epidemiol Biomarkers Prev. 2005 Apr;14(4):863-70 [15824157.001]

[Cites] Cell Cycle. 2005 Apr;4(4):521-5 [15753653.001]

[Cites] Am J Gastroenterol. 2005 Jun;100(6):1376-80 [15929773.001]

[Cites] Cancer Res. 2005 Aug 15;65(16):7516-22 [16103107.001]

[Cites] Cancer Causes Control. 2005 Oct;16(8):965-73 [16132805.001]

[Cites] Mutat Res. 2005 Dec 30;592(1-2):147-54 [16054167.001]

[Cites] Nucleic Acids Res. 2006 Jan 1;34(Database issue):D617-21 [16381944.001]

[Cites] Am J Gastroenterol. 2005 Dec;100(12):2789-95 [16393237.001]

[Cites] Cancer Epidemiol Biomarkers Prev. 2006 Nov;15(11):2325-7 [17119068.001]

[Cites] Oncogene. 2006 Dec 4;25(57):7531-7 [17143297.001]

[Cites] Gut. 2007 Mar;56(3):417-25 [16840506.001]

[Cites] Breast Cancer Res. 2007;9(2):R27 [17428325.001]

[Cites] JAMA. 2007 Jun 6;297(21):2351-9 [17551129.001]

[Cites] Am J Clin Nutr. 2007 Jun;85(6):1592-7 [17556698.001]

[Cites] Gastroenterology. 2008 Jan;134(1):56-64 [18166348.001]

(PMID = 20510605.001).

[ISSN] 1879-0852

[Journal-full-title] European journal of cancer (Oxford, England : 1990)

[ISO-abbreviation] Eur. J. Cancer

[Language] eng

[Grant] United States / Intramural NIH HHS / / Z01 HG000120-12

[Publication-type] Journal Article; Multicenter Study; Research Support, N.I.H., Intramural

[Publication-country] England

[Chemical-registry-number] 0 / Dietary Fats

[Other-IDs] NLM/ NIHMS202303; NLM/ PMC2924917

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] The adenomatous polyposis coli protein (APC) exists in two distinct soluble complexes with different functions.

Mutations resulting in the truncation of the adenomatous polyposis coli (APC) protein are common to most colonic tumours.

The APC protein has emerged as a multifunctional protein that contributes to cytoskeletal organisation and is involved in the regulation of beta-catenin.

Both, changes in transcription due to increases in beta-catenin, as well as defects in directed cell migration and cell division contribute to cancer when APC is mutated.

Little is known about how separate functions of APC are coordinated.

In this study, we identified two distinct soluble protein pools containing APC.

The second pool contained at least two different forms of APC: APC that was bound to partially assembled beta-catenin-targeting complexes and APC that could bind microtubules.

Similarly, tumour cells with truncated APC only contained the partially assembly beta-catenin-targeting complex.

We also found that highly elevated levels of beta-catenin in tumour cells containing wild-type APC correlated with a decrease in the ability of the endogenous APC protein to bind microtubules.

Additionally, APC lacking the direct microtubule binding site was more effective at downregulating beta-catenin.

Together, our data suggest that the interaction of APC with microtubules and the beta-catenin-targeting complex are mutually exclusive, and indicate that the distribution of endogenous APC between different pools is dynamic, which allows cells to distribute it as required.

[MeSH-major] Adenomatous Polyposis Coli Protein / chemistry. Adenomatous Polyposis Coli Protein / metabolism

[MeSH-minor] Animals. Axin Protein. Cell Line. Centrifugation, Density Gradient. Enzyme Inhibitors / pharmacology. Glycogen Synthase Kinase 3 / analysis. Glycogen Synthase Kinase 3 / antagonists & inhibitors. Glycogen Synthase Kinase 3 / metabolism. Humans. Macromolecular Substances / chemistry. Macromolecular Substances / metabolism. Microtubules / metabolism. Protein Binding. Repressor Proteins / metabolism. Solubility. beta Catenin / analysis

Genetic Alliance. consumer health - Familial Adenomatous Polyposis (FAP).

Gene Ontology. gene/protein/disease-specific - Gene Ontology annotations from this paper .

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 16188939.001).

[ISSN] 0021-9533

[Journal-full-title] Journal of cell science

[ISO-abbreviation] J. Cell. Sci.

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] England

[Chemical-registry-number] 0 / Adenomatous Polyposis Coli Protein; 0 / Axin Protein; 0 / Enzyme Inhibitors; 0 / Macromolecular Substances; 0 / Repressor Proteins; 0 / beta Catenin; EC 2.7.11.26 / Glycogen Synthase Kinase 3

   

Advertisement

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] The adenomatous polyposis coli tumor suppressor and Wnt signaling in the regulation of apoptosis.

The adenomatous polyposis coli (APC) tumor suppressor is an essential negative regulator in the evolutionarily conserved Wnt/Wingless (Wg) signal transduction pathway.

During normal development, Wnt signaling is required not only to induce cell proliferation and cell fate specification, but also to induce apoptotic cell death.

However in some malignant states triggered by APC loss, inappropriate activation of Wnt signaling promotes cell survival and inhibits cell death, indicating that the cellular response to APC loss and Wnt signaling is highly dependent on cell context.

This chapter summarizes our current understanding of the role of APC and Wnt signaling in the regulation of apoptosis, based upon studies from fly and mouse in vivo models, as well as cultured carcinoma cells.

[Email] Email this result item

Email the results to the following email address:   [X] Close

[Cites] Br J Cancer. 1999 Oct;81(3):496-502 [10507776.001]

[Cites] Nat Rev Mol Cell Biol. 2004 Nov;5(11):897-907 [15520809.001]

[Cites] Nat Rev Genet. 2004 Dec;5(12):911-22 [15573123.001]

[Cites] Mol Cell Biol. 2005 Feb;25(4):1475-88 [15684397.001]

[Cites] J Pediatr. 2005 Aug;147(2):263-6 [16126064.001]

[Cites] J Cell Biol. 2002 Apr 29;157(3):429-40 [11980918.001]

[Cites] Mol Pathol. 2002 Aug;55(4):220-6 [12147710.001]

[Cites] Science. 2002 Aug 2;297(5582):848-51 [12161657.001]

[Cites] Cell. 2002 Oct 18;111(2):241-50 [12408868.001]

[Cites] Cell. 2002 Oct 18;111(2):251-63 [12408869.001]

[Cites] Nat Genet. 2002 Dec;32(4):594-605 [12426568.001]

[Cites] Int J Oncol. 2003 Jan;22(1):209-12 [12469206.001]

[Cites] Mol Biol Cell. 2003 Jul;14(7):2844-60 [12857869.001]

[Cites] Cancer Res. 2003 Aug 1;63(15):4368-74 [12907606.001]

[Cites] Am J Med Genet A. 2003 Nov 1;122A(4):335-41 [14518072.001]

[Cites] Dev Cell. 2003 Nov;5(5):799-809 [14602079.001]

[Cites] Science. 2004 Feb 13;303(5660):1020-3 [14716020.001]

[Cites] Nat Genet. 2004 Apr;36(4):417-22 [15034581.001]

[Cites] Neoplasia. 2004 Jan-Feb;6(1):7-14 [15068666.001]

[Cites] Am J Gastroenterol. 2004 Apr;99(4):681-6 [15089902.001]

[Cites] Development. 2004 May;131(10):2409-18 [15128670.001]

[Cites] Cancer Res. 2004 May 15;64(10):3474-8 [15150100.001]

[Cites] Genes Dev. 2004 Jun 15;18(12):1385-90 [15198980.001]

[Cites] Cancer Res. 2004 Aug 1;64(15):5385-9 [15289346.001]

[Cites] Oncogene. 2004 Aug 12;23(36):6170-4 [15208662.001]

[Cites] Int J Dev Biol. 2004;48(5-6):377-86 [15349813.001]

[Cites] Mech Dev. 2004 Dec;121(12):1523-30 [15511643.001]

[Cites] Am J Ophthalmol. 1975 Feb;79(2):177-89 [1115190.001]

[Cites] Am J Ophthalmol. 1980 Nov;90(5):661-7 [7446647.001]

[Cites] Am J Ophthalmol. 1990 Nov 15;110(5):550-61 [2173407.001]

[Cites] Cell. 1991 Aug 9;66(3):589-600 [1651174.001]

[Cites] Cell. 1991 Aug 9;66(3):601-13 [1678319.001]

[Cites] Curr Opin Cell Biol. 2005 Dec;17(6):617-25 [16243507.001]

[Cites] Curr Biol. 2006 May 23;16(10):R378-85 [16713950.001]

[Cites] Genes Dev. 2006 Jun 1;20(11):1394-404 [16751178.001]

[Cites] Int Rev Cytol. 2006;251:131-58 [16939779.001]

[Cites] Cell Death Differ. 2007 Jan;14(1):66-72 [17082814.001]

[Cites] Nat Genet. 2000 Mar;24(3):245-50 [10700176.001]

[Cites] Bioessays. 2000 Aug;22(8):708-16 [10918301.001]

[Cites] Mol Biol Cell. 2000 Oct;11(10):3509-23 [11029052.001]

[Cites] BMC Cancer. 2006;6:221 [16959035.001]

[Cites] Cell. 2006 Nov 3;127(3):469-80 [17081971.001]

[Cites] Front Biosci. 2007;12:471-91 [17127311.001]

[Cites] Nat Cell Biol. 1999 Jul;1(3):144-51 [10559900.001]

[Cites] J Cell Biol. 2001 Jan 8;152(1):87-96 [11149923.001]

[Cites] EMBO Rep. 2001 Feb;2(2):157-62 [11258709.001]

[Cites] Cancer Lett. 2001 May 26;166(2):185-91 [11311491.001]

[Cites] Gastroenterology. 2001 Jul;121(1):198-213 [11438509.001]

[Cites] Nat Immunol. 2001 Aug;2(8):691-7 [11477404.001]

[Cites] Int J Oncol. 2001 Nov;19(5):1003-7 [11605001.001]

[Cites] Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):297-302 [11756652.001]

[Cites] J Pathol. 2002 Feb;196(2):145-53 [11793365.001]

[Cites] Development. 2002 Apr;129(7):1751-62 [11923210.001]

[Cites] J Biol Chem. 2002 May 3;277(18):15843-50 [11854293.001]

[Cites] Science. 1991 Aug 9;253(5020):661-5 [1651562.001]

[Cites] Science. 1991 Aug 9;253(5020):665-9 [1651563.001]

[Cites] Proc Natl Acad Sci U S A. 1992 May 15;89(10):4452-6 [1316610.001]

[Cites] Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2846-50 [8385345.001]

[Cites] N Engl J Med. 1993 Dec 30;329(27):1982-7 [8247073.001]

[Cites] Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7950-4 [8755583.001]

[Cites] Cell. 1996 Oct 18;87(2):159-70 [8861899.001]

[Cites] Arch Ophthalmol. 1997 May;115(5):645-50 [9152133.001]

[Cites] Nature. 1997 Oct 30;389(6654):966-70 [9353119.001]

[Cites] J Cell Biol. 1998 May 4;141(3):765-77 [9566975.001]

[Cites] J Pediatr Hematol Oncol. 1998 May-Jun;20(3):274-8 [9628444.001]

[Cites] Cell. 1998 Jun 26;93(7):1171-82 [9657150.001]

[Cites] Nature. 1998 Nov 26;396(6709):370-3 [9845073.001]

[Cites] Dev Biol. 1999 Feb 15;206(2):178-88 [9986731.001]

[Cites] J Cell Biol. 1999 Sep 20;146(6):1303-18 [10491393.001]

(PMID = 19928354.001).

[ISSN] 0065-2598

[Journal-full-title] Advances in experimental medicine and biology

[ISO-abbreviation] Adv. Exp. Med. Biol.

[Language] ENG

[Grant] United States / NCI NIH HHS / CA / CA105038-04; United States / NCI NIH HHS / CA / R01 CA105038; United States / NCI NIH HHS / CA / R01 CA105038-04; United States / NCI NIH HHS / CA / R01CA105038; United States / Howard Hughes Medical Institute / /

[Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review

[Publication-country] United States

[Chemical-registry-number] 0 / Adenomatous Polyposis Coli Protein; 0 / Wnt Proteins

[Number-of-references] 71

[Other-IDs] NLM/ NIHMS279106; NLM/ PMC3066060

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Multiple rare nonsynonymous variants in the adenomatous polyposis coli gene predispose to colorectal adenomas.

It has been proposed that multiple rare variants in numerous genes collectively account for a substantial proportion of multifactorial inherited predisposition to a variety of diseases, including colorectal adenomas (CRA).

We have studied this hypothesis by sequencing the adenomatous polyposis coli (APC) gene in 691 unrelated North American patients with CRAs and 969 matched healthy controls.

Rare inherited nonsynonymous variants of APC were significantly overrepresented in patients who did not carry conventional pathogenic mutations in the APC or MutY homologue genes [non-familial adenomatous polyposis (FAP) non-MUTYH-associated polyposis (MAP) patients; 81 of 480, 16.9%] compared with patients with FAP or MAP (20 of 211, 9.5%, P = 0.0113), and this overrepresentation was highest in those non-FAP non-MAP patients with 11 to 99 CRAs (30 of 161, 18.6%, P = 0.0103).

Furthermore, significantly more non-FAP non-MAP patients carried rare nonsynonymous variants in the functionally important beta-catenin down-regulating domain compared with healthy controls (32 of 480 versus 37 of 969, P = 0.0166).

These data suggest that multiple rare nonsynonymous variants in APC play a significant role in predisposing to CRAs.

[MeSH-major] Adenoma / genetics. Adenomatous Polyposis Coli Protein / genetics. Colorectal Neoplasms / genetics. Genetic Predisposition to Disease. Polymorphism, Single Nucleotide

[MeSH-minor] Adult. Case-Control Studies. DNA Mutational Analysis. Down-Regulation. Female. Humans. Male. Middle Aged. Protein Structure, Tertiary. beta Catenin / metabolism

Genetic Alliance. consumer health - Familial Adenomatous Polyposis (FAP).

MedlinePlus Health Information. consumer health - Colorectal Cancer.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 18199528.001).

[ISSN] 1538-7445

[Journal-full-title] Cancer research

[ISO-abbreviation] Cancer Res.

[Language] eng

[Grant] United Kingdom / Medical Research Council / / G0301154

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] United States

[Chemical-registry-number] 0 / Adenomatous Polyposis Coli Protein; 0 / beta Catenin

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] A novel function of adenomatous polyposis coli (APC) in regulating DNA repair.

Prevailing literature suggests diversified cellular functions for the adenomatous polyposis coli (APC) gene.

Among them a recently discovered unique role of APC is in DNA repair.

The APC gene can modulate the base excision repair (BER) pathway through an interaction with DNA polymerase beta (Pol-beta) and flap endonuclease 1 (Fen-1).

Taken together with the transcriptional activation of APC gene by alkylating agents and modulation of BER activity, APC may play an important role in carcinogenesis and chemotherapy by determining whether cells with DNA damage survive or undergo apoptosis.

Genetic Alliance. consumer health - Familial Adenomatous Polyposis (FAP).

COS Scholar Universe. author profiles.

[Email] Email this result item

Email the results to the following email address:   [X] Close

[Cites] Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11450-4 [1722334.001]

[Cites] Cancer Res. 1992 Jul 15;52(14):4055-7 [1319838.001]

[Cites] Cancer Res. 1992 Sep 1;52(17):4824-7 [1511447.001]

[Cites] Nature. 1992 Sep 17;359(6392):235-7 [1528264.001]

[Cites] Science. 1993 May 7;260(5109):816-9 [8484122.001]

[Cites] Hum Mol Genet. 1992 Jul;1(4):229-33 [1338904.001]

[Cites] Cancer Res. 1994 Jul 15;54(14):3672-5 [8033082.001]

[Cites] Cancer Res. 1994 Jul 15;54(14):3676-81 [8033083.001]

[Cites] Am J Pathol. 1994 Sep;145(3):531-4 [8080037.001]

[Cites] Science. 1995 Aug 4;269(5224):699-702 [7624801.001]

[Cites] J Biol Chem. 1996 Jul 26;271(30):17811-5 [8663612.001]

[Cites] Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9588-93 [8790374.001]

[Cites] Biochemistry. 1996 Oct 1;35(39):12778-87 [8841120.001]

[Cites] J Biol Chem. 1997 Jan 10;272(2):1302-7 [8995436.001]

[Cites] J Cell Biol. 1997 Feb 10;136(3):693-706 [9024698.001]

[Cites] J R Coll Physicians Lond. 1997 Jan-Feb;31(1):82-9 [9044206.001]

[Cites] Cell. 2004 Jan 9;116(1):39-50 [14718165.001]

[Cites] Mol Cancer. 2003 Dec 12;2:41 [14672538.001]

[Cites] J Comput Chem. 2004 Oct;25(13):1605-12 [15264254.001]

[Cites] Cancer. 1975 Dec;36(6):2251-70 [1203876.001]

[Cites] Proc Natl Acad Sci U S A. 1978 Jan;75(1):346-50 [203936.001]

[Cites] J Biol Chem. 1981 Apr 10;256(7):3405-14 [6259165.001]

[Cites] Annu Rev Biochem. 1988;57:29-67 [3052275.001]

[Cites] J Biol Chem. 2005 Feb 25;280(8):6942-9 [15548520.001]

[Cites] Bioessays. 2005 Jul;27(7):717-29 [15954100.001]

[Cites] Mol Biol Cell. 2005 Oct;16(10):4609-22 [16030254.001]

[Cites] DNA Repair (Amst). 2005 Dec 8;4(12):1347-57 [16172026.001]

[Cites] Carcinogenesis. 1999 Jun;20(6):1049-54 [10357787.001]

[Cites] Oncogene. 1999 May 6;18(18):2883-91 [10362259.001]

[Cites] DNA Cell Biol. 1999 Jul;18(7):549-54 [10433553.001]

[Cites] Nat Med. 1999 Sep;5(9):1071-5 [10470088.001]

[Cites] J Biol Chem. 1999 Nov 19;274(47):33696-702 [10559260.001]

[Cites] Br J Cancer. 2000 Jan;82(2):348-53 [10646887.001]

[Cites] Oncogene. 2000 Jan 20;19(3):365-72 [10656683.001]

[Cites] Science. 1997 Mar 21;275(5307):1784-7 [9065401.001]

[Cites] Science. 1997 Mar 21;275(5307):1787-90 [9065402.001]

[Cites] Science. 1997 Mar 21;275(5307):1790-2 [9065403.001]

[Cites] Bioessays. 1997 Mar;19(3):233-40 [9080773.001]

[Cites] J Biol Chem. 1997 Feb 21;272(8):4647-50 [9081985.001]

[Cites] Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3034-9 [9096341.001]

[Cites] Biochem J. 1997 Jul 1;325 ( Pt 1):1-16 [9224623.001]

[Cites] EMBO J. 1997 Jun 2;16(11):3341-8 [9214649.001]

[Cites] J Biol Chem. 1997 Dec 5;272(49):30619-22 [9388195.001]

[Cites] J Biol Chem. 1998 Jan 9;273(2):898-902 [9422747.001]

[Cites] J Biol Chem. 1998 Apr 10;273(15):8842-8 [9535864.001]

[Cites] J Biol Chem. 1998 May 1;273(18):11121-6 [9556598.001]

[Cites] Mutat Res. 1998 May 25;400(1-2):59-68 [9685584.001]

[Cites] Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10722-7 [9724771.001]

[Cites] Science. 1998 Sep 4;281(5382):1509-12 [9727977.001]

[Cites] Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1603-8 [9990071.001]

[Cites] Proc Natl Acad Sci U S A. 1999 May 11;96(10):5522-7 [10318916.001]

[Cites] Genes Dev. 1999 May 15;13(10):1309-21 [10346819.001]

[Cites] J Biol Chem. 2000 Apr 7;275(14):10463-71 [10744736.001]

[Cites] J Clin Oncol. 2000 May;18(9):1967-79 [10784639.001]

[Cites] Nat Cell Biol. 2001 Apr;3(4):433-8 [11283620.001]

[Cites] Nature. 2001 May 17;411(6835):366-74 [11357144.001]

[Cites] J Biol Chem. 2001 May 25;276(21):18193-9 [11279192.001]

[Cites] Curr Biol. 2001 Jul 10;11(13):1062-7 [11470413.001]

[Cites] J Biol Chem. 2002 Jan 4;277(1):630-8 [11677229.001]

[Cites] J Biol Chem. 2002 Sep 20;277(38):35550-60 [12121998.001]

[Cites] Br Med Bull. 2002;64:27-43 [12421723.001]

[Cites] Carcinogenesis. 2006 Feb;27(2):252-61 [16150893.001]

[Cites] Chem Rev. 2006 Feb;106(2):361-82 [16464010.001]

[Cites] Biochemistry. 2006 Dec 26;45(51):15903-14 [17176113.001]

[Cites] Oncogene. 2007 Mar 1;26(10):1428-38 [16924228.001]

[Cites] Curr Opin Cell Biol. 2007 Apr;19(2):150-8 [17306971.001]

[Cites] Carcinogenesis. 2007 Oct;28(10):2089-95 [17522063.001]

[Cites] Biochemistry. 2007 Dec 11;46(49):13961-74 [17999539.001]

[Cites] Mutat Res. 2000 Jun 30;451(1-2):39-51 [10915864.001]

[Cites] Genes Dev. 2000 Aug 1;14(15):1837-51 [10921899.001]

[Cites] FASEB J. 2000 Sep;14(12):1765-74 [10973926.001]

[Cites] Nature. 2000 Aug 31;406(6799):1009-12 [10984057.001]

[Cites] Nat Cell Biol. 2000 Sep;2(9):653-60 [10980707.001]

[Cites] Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12085-90 [11035805.001]

[Cites] J Cell Biochem. 2001 Mar 26;81(2):262-77 [11241666.001]

[Cites] EMBO J. 2001 Mar 15;20(6):1477-82 [11250913.001]

[Cites] Hum Mol Genet. 2001 Apr;10(7):721-33 [11257105.001]

[Cites] Annu Rev Pharmacol Toxicol. 2001;41:367-401 [11264462.001]

[Cites] Nat Cell Biol. 2001 Apr;3(4):429-32 [11283619.001]

[Cites] Cell. 1990 Jun 1;61(5):759-67 [2188735.001]

(PMID = 18662849.001).

[ISSN] 1872-7980

[Journal-full-title] Cancer letters

[ISO-abbreviation] Cancer Lett.

[Language] ENG

[Grant] United States / NCI NIH HHS / CA / CA-100247; United States / NCI NIH HHS / CA / R01 CA100247-01; United States / NCI NIH HHS / CA / CA100247-01; United States / NCI NIH HHS / CA / R01 CA097031-01A1; United States / NCI NIH HHS / CA / CA-097031; United States / NCI NIH HHS / CA / CA097031-01A1; United States / NCI NIH HHS / CA / R01 CA097031; United States / NCI NIH HHS / CA / R01 CA100247

[Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review

[Publication-country] Ireland

[Chemical-registry-number] 0 / Alkylating Agents; EC 2.7.7.- / DNA Polymerase beta; EC 3.1.- / Flap Endonucleases

[Number-of-references] 81

[Other-IDs] NLM/ NIHMS78341; NLM/ PMC2585005

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Involvement of adenomatous polyposis coli in colorectal tumorigenesis.

Mutation in the adenomatous polyposis coli (APC) gene is considered to be one of the earliest events in the colon cancer development.

The familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC) are the most commonly inherited colorectal cancers.

FAP and HNPCC develop due to mutations in APC and DNA mismatch repair (MMR) genes, respectively.

APC is known to regulate the levels of beta-catenin, an important mediator of cell-cell adhesion and transcriptional regulator.

Mutations in APC gene are also linked with chromosomal instability in colon cancer cells.

The role of APC is also implicated in cell migration, cell-cell adhesion, cell cycle control, and apoptosis.

This article summarizes the structure-function studies and the role of APC mutations in colon cancer development.

[MeSH-major] Adenomatous Polyposis Coli / physiopathology. Adenomatous Polyposis Coli Protein / physiology. Colorectal Neoplasms / etiology

Genetic Alliance. consumer health - Familial Adenomatous Polyposis (FAP).

Genetics Home Reference. consumer health - APC gene.

MedlinePlus Health Information. consumer health - Colorectal Cancer.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 15769611.001).

[ISSN] 1093-9946

[Journal-full-title] Frontiers in bioscience : a journal and virtual library

[ISO-abbreviation] Front. Biosci.

[Language] eng

[Grant] United States / NCI NIH HHS / CA / CA-097031; United States / NCI NIH HHS / CA / CA-100247

[Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review

[Publication-country] United States

[Chemical-registry-number] 0 / Adenomatous Polyposis Coli Protein; 0 / beta Catenin

[Number-of-references] 174

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Implication of adenomatous polyposis coli and MUTYH mutations in familial colorectal polyposis.

PURPOSE: Familial adenomatous polyposis is an autosomal dominantly inherited syndrome characterized by hundreds or thousands of colorectal polyps and a high risk of colorectal cancer at a young age.

Truncating germline mutations in the adenomatous polyposis coli gene are detected in approximately 80 percent of patients with classical familial adenomatous polyposis and in approximately 10 percent of the attenuated familial adenomatous polyposis patients.

METHODS: We investigated the adenomatous polyposis coli and MUTYH genes mutations in a well-characterized series of 25 unrelated Italian patients with familial adenomatous polyposis.

RESULTS: We characterized the specific adenomatous polyposis coli gene mutation in 10 probands, and identified eight truncating mutations (4 novel and 4 known mutations) and two splicing mutations.

Moreover, 11 MUTYH gene mutations have been identified in 7 patients without a dominant family history of polyposis.

CONCLUSIONS: This study enlarges the genotype-phenotype correlations of familial adenomatous polyposis and suggests that messenger alterations could be responsible for a subset of familial adenomatous polyposis cases without germ-line adenomatous polyposis coli or MUTYH gene mutations.

It also confirms that genotype-phenotype correlations in MUTYH-associated polyposis are very complex.

[MeSH-major] Adenomatous Polyposis Coli / genetics. DNA Glycosylases / genetics. Mutation

[MeSH-minor] Adolescent. Genes, APC. Genotype. Humans. Male. Middle Aged. Sequence Analysis, DNA

Genetic Alliance. consumer health - Familial Adenomatous Polyposis (FAP).

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 19279422.001).

[ISSN] 1530-0358

[Journal-full-title] Diseases of the colon and rectum

[ISO-abbreviation] Dis. Colon Rectum

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] United States

[Chemical-registry-number] EC 3.2.2.- / DNA Glycosylases; EC 3.2.2.- / mutY adenine glycosylase

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Immunohistochemical detection of beta-catenin and adenomatous polyposis coli in ameloblastomas.

BACKGROUND: To clarify the roles of the Wnt signaling pathway in oncogenesis and cytodifferentiation of odontogenic tumors, expression of beta-catenin and adenomatous polyposis coli (APC) was analyzed in ameloblastomas as well as in tooth germs.

METHODS: Tissue specimens of 10 tooth germs, 40 benign ameloblastomas, and five malignant ameloblastomas were examined immunohistochemically with the use of antibodies against beta-catenin and APC.

Nuclear beta-catenin expression was recognized in nine of 40 ameloblastomas and two of five malignant ameloblastomas, but not in tooth germs.

APC was evidently expressed in odontogenic epithelial cells neighboring the basement membrane in tooth germs and ameloblastomas, and the reactivity was significantly lower in benign and malignant ameloblastomas than in tooth germs.

Follicular ameloblastomas and acanthomatous ameloblastomas tended to show high nuclear beta-catenin expression and low APC reactivity, as compared with other ameloblastoma variants.

CONCLUSION: Expression of beta-catenin and APC in tooth germs and ameloblastomas suggests that aberration of the Wnt signaling pathway might play a role in oncogenesis and cytodifferentiation of odontogenic epithelium via deregulation of cell proliferation.

[MeSH-major] Adenomatous Polyposis Coli Protein / analysis. Ameloblastoma / chemistry. Cytoskeletal Proteins / analysis. Jaw Neoplasms / chemistry. Trans-Activators / analysis

Genetic Alliance. consumer health - Familial Adenomatous Polyposis (FAP).

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 16011608.001).

[ISSN] 0904-2512

[Journal-full-title] Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology

[ISO-abbreviation] J. Oral Pathol. Med.

[Language] eng

[Publication-type] Journal Article

[Publication-country] Denmark

[Chemical-registry-number] 0 / Adenomatous Polyposis Coli Protein; 0 / CTNNB1 protein, human; 0 / CTNNB1 protein, mouse; 0 / Cytoskeletal Proteins; 0 / Trans-Activators; 0 / beta Catenin

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Truncation mutations abolish chromatin-associated activities of adenomatous polyposis coli.

The adenomatous polyposis coli (APC) is a tumor suppressor whose loss of function leads to colon cancer.

APC shuttles between the nucleus and cytoplasm, however its role in the nucleus remains elusive.

We have found that nuclear APC specifically associates with transcriptionally active chromatin through structural elements located downstream to the region of frequent truncation mutations found in colorectal tumors.

We show that a recombinant APC fragment comprising such elements associates in vivo with euchromatin and preferentially binds in vitro to acetylated histone H3.

Induction of DNA double-strand breaks (DSB) stimulates accumulation of APC at the damaged DNA chromatin marked by histone H2AX and S139-phosphorylated histone H2AX.

A nuclear complex containing the DNA-dependent protein kinase catalytic subunit (DNAPKcs) and APC associates with chromatin in response to DNA DSB.

APC knockdown with siRNA decreased the rate of DNA DSB-induced S139 histone H2AX phosphorylation in cells expressing endogenous full-length APC, but not in colon cancer cells with its truncation mutants, whereas ectopic APC expression stimulated the H2AX phosphorylation regardless of the type of endogenous APC.

Our data suggest that APC involves in the DSB DNA repair and that truncation mutations impair chromatin-associated functions of APC.

[MeSH-major] Adenomatous Polyposis Coli / physiopathology. Chromatin / metabolism. Mutation

[MeSH-minor] Binding Sites. Cell Line. DNA Damage. DNA Repair. Genes, APC. Histone Acetyltransferases / metabolism. Humans. Transcriptional Activation

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 18454178.001).

[ISSN] 1476-5594

[Journal-full-title] Oncogene

[ISO-abbreviation] Oncogene

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] England

[Chemical-registry-number] 0 / Chromatin; EC 2.3.1.48 / Histone Acetyltransferases

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Non-traditional roles for the Adenomatous Polyposis Coli (APC) tumor suppressor protein.

The Adenomatous Polyposis Coli (APC) tumor suppressor is a multifunctional protein that is mutated in a majority of colon cancers.

The role of APC as an antagonist of the Wnt signaling pathway is well known and it is widely accepted that inappropriate activation of this pathway through loss of APC function contributes to the progression of colon cancers.

However, a body of evidence is growing to support the idea that APC plays non-traditional functions outside of the Wnt pathway with roles in cell migration, adhesion, chromosome segregation, spindle assembly, apoptosis, and neuronal differentiation.

This review highlights the research into alternate functions for APC beyond its role in Wnt signaling and discusses the possible contributions for these non-traditional functions of APC in tumor formation.

[MeSH-major] Adenomatous Polyposis Coli Protein / physiology

[MeSH-minor] Animals. Apoptosis / physiology. Cell Adhesion / physiology. Cell Cycle / physiology. Cell Movement / physiology. Humans. Microtubules / metabolism. Protein Binding. Spindle Apparatus / physiology. beta Catenin / metabolism

Genetic Alliance. consumer health - Familial Adenomatous Polyposis (FAP).

COS Scholar Universe. author profiles.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 16185824.001).

[ISSN] 0378-1119

[Journal-full-title] Gene

[ISO-abbreviation] Gene

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review

[Publication-country] Netherlands

[Chemical-registry-number] 0 / Adenomatous Polyposis Coli Protein; 0 / beta Catenin

[Number-of-references] 106

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Detection of cytoplasmic and nuclear localization of adenomatous polyposis coli (APC) protein in cells.

The adenomatous polyposis coli (APC) tumour suppressor gene is mutated in the majority of colon cancers.

APC is a multi-domain protein whose distribution at different subcellular locations correlates with unique cellular processes.

Our laboratory has focused on the link between APC subcellular location and function, and has characterized pathways for the trafficking of APC both into and out of the nucleus.

Antibody specificity is an important factor in the determination of APC localization, and in this chapter we outline a strategy for the unambiguous detection of APC using a combination of biochemical and cell biology approaches.

[MeSH-major] Adenomatous Polyposis Coli Protein / metabolism. Cell Nucleus / metabolism. Cytoplasm / metabolism. Subcellular Fractions / metabolism

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 19099247.001).

[ISSN] 1064-3745

[Journal-full-title] Methods in molecular biology (Clifton, N.J.)

[ISO-abbreviation] Methods Mol. Biol.

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] United States

[Chemical-registry-number] 0 / Adenomatous Polyposis Coli Protein

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Mutations of APC and MYH in unrelated Italian patients with adenomatous polyposis coli.

The analysis of APC and MYH mutations in adenomatous polyposis coli patients should provide clues about the genetic heterogeneity of the syndrome in human populations.

The entire coding region and intron-exon borders of the APC and MYH genes were analyzed in 60 unrelated Italian adenomatous polyposis coli patients.

APC analysis revealed 26 point mutations leading to premature termination, one missense variant and one deletion spanning the entire coding region in 32 unrelated patients.

Novel truncating point mutations included c.1176_1177insT (p.His393_PhefsX396), c.1354_1355del (p.Val452_SerfsX458), c.2684C>A (p.Ser895X), c.2711_2712del (p.Arg904_LysfsX910), c.2758_2759del (p.Asp920_CysfsX922), c.4192_4193del (p.Ser1398_SerfsX1407), c.4717G>T (p.Glu1573X) and a novel cryptic APC exon 6 splice site.

MYH analysis revealed nine different germline variants in nine patients, of whom five were homozygotes or compound heterozygotes.

The mutations included 4 novel MYH missense variants (c.692G>A, p.Arg231His; c.778C>T, p.Arg260Trp; c.1121T>C, p.Leu374Pro; and c.1234C>T, p.Arg412Cys) affecting conserved amino acid residues in the ENDO3c or NUDIX domains of the protein and one novel synonymous change (c.672C>T, p.Asn224Asn).

Genotype-phenotype correlations were found in carriers of APC mutations but not in carriers of biallelic MYH mutations, except for a negative correlation with low number of polyps.

A distinctive characteristic of patients negative for APC and MYH mutations was a significantly (p<0.0001) older age at diagnosis compared to patients with APC mutations.

Moreover, the proportion of cases with an attenuated polyposis phenotype was higher (p = 0.0008) among patients negative for APC and MYH mutations than among carriers of APC or biallelic MYH mutations.

[MeSH-major] Adenomatous Polyposis Coli / genetics. DNA Glycosylases / genetics. Genes, APC. Mutation

[MeSH-minor] Colorectal Neoplasms / genetics. Genetic Predisposition to Disease. Genetic Variation. Genotype. Humans. Italy. Phenotype

[Email] Email this result item

Email the results to the following email address:   [X] Close

[Copyright] (c) 2005 Wiley-Liss, Inc.

(PMID = 16134147.001).

[ISSN] 1098-1004

[Journal-full-title] Human mutation

[ISO-abbreviation] Hum. Mutat.

[Language] eng

[Databank-accession-numbers] OMIM/ 175100/ 604933/ 608456

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] United States

[Chemical-registry-number] EC 3.2.2.- / DNA Glycosylases; EC 3.2.2.- / mutY adenine glycosylase

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] [Germline mutation of adenomatous polyposis coli gene in Chinese patients with familial adenomatous polyposis].

OBJECTIVE: To explore the characteristics of adenomatous polyposis coli (APC) gene germline mutations in Chinese patients with familial adenomatous polyposis (FAP).

METHODS: Eighteen members from nine FAP pedigrees were studied by using multiplex ligation-dependent probe amplification(MLPA) to detect large fragment deletion of APC gene.

Then, PCR were performed to amplify all exons of APC gene for mutation screening by denaturing high performance liquid chromatography (DHPLC).

They were c.3184_3187 del CAAA in pedigree 2, c.5432C to T in pedigree 4 and c.3925_3929 del AAAAG in pedigree 9 respectively.

CONCLUSION: APC gene germline mutations can cause the development of FAP.

The FAP patients without APC gene germline mutations could be caused by other mechanisms.

[MeSH-major] Adenomatous Polyposis Coli / genetics. Genes, APC / physiology

[MeSH-minor] Adult. Chromatography, High Pressure Liquid. Female. Genetic Predisposition to Disease / genetics. Germ-Line Mutation. Humans. Male. Middle Aged. Pedigree

Genetic Alliance. consumer health - Familial Adenomatous Polyposis (FAP).

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 18393246.001).

[ISSN] 1003-9406

[Journal-full-title] Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics

[ISO-abbreviation] Zhonghua Yi Xue Yi Chuan Xue Za Zhi

[Language] chi

[Publication-type] English Abstract; Journal Article

[Publication-country] China

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Methylation analysis of the adenomatous polyposis coli (APC) gene in adult T-cell leukemia/lymphoma.

We investigated methylation status of the adenomatous polyposis coli (APC) gene in adult T-cell leukemia/lymphoma (ATL).

APC methylation was found in 15 of 31 (48%) primary samples, and 2 of 4 (50%) ATL cell lines.

Methylation of the APC gene occurred more frequently in acute ATL (12/21) (57%) than chronic ATL (1/8) (13%) (P = 0.03).

APC was not expressed in the APC-methylated ATL cell line ST1.

Demethylation with 5-azacytidine treatment restored APC expression in the ST1 cell line.

Our data show that hypermethylation of the APC gene is involved in the pathogenesis of ATL.

[MeSH-major] Adenomatous Polyposis Coli Protein / genetics. DNA Methylation. Leukemia-Lymphoma, Adult T-Cell / genetics

[MeSH-minor] Azacitidine / pharmacology. Cell Line, Tumor. CpG Islands / genetics. Disease Progression. Humans. Promoter Regions, Genetic. Reverse Transcriptase Polymerase Chain Reaction

Genetic Alliance. consumer health - Familial Adenomatous Polyposis (FAP).

[Email] Email this result item

Email the results to the following email address:   [X] Close

[CommentIn] Leuk Res. 2005 May;29(5):475-6 [15755498.001]

(PMID = 15541474.001).

[ISSN] 0145-2126

[Journal-full-title] Leukemia research

[ISO-abbreviation] Leuk. Res.

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.

[Publication-country] England

[Chemical-registry-number] 0 / Adenomatous Polyposis Coli Protein; M801H13NRU / Azacitidine

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Polymorphisms in the adenomatous polyposis coli gene in Slovak families suspected of FAP.

OBJECTIVES: Polymorphism in the adenomatous polyposis coli (APC) gene was analyzed in 33 families suspected of familial adenomatous polyposis (FAP) without identified APC gene mutation.

Screening of 104 members of mentioned families for polymorphism in the APC gene, was performed using single strand conformation polymorphism (SSCP) and DNA sequencing.

CONCLUSION: The most frequently detected polymorphism D1822V is potentially associated with the risk of colorectal cancer.

Three detected polymorphisms - Y486Y, T1493T and S1756S - also seem to be associated with colon cancer risk.

All these polymorphisms may be used as markers for diagnosis of colorectal cancer.

[MeSH-major] Adenomatous Polyposis Coli / genetics. Genes, APC. Polymorphism, Genetic

[MeSH-minor] Cohort Studies. Exons. Family. Genetic Predisposition to Disease. Humans. Mutation. Polymorphism, Single-Stranded Conformational. Sequence Analysis, DNA. Slovakia

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 20027139.001).

[ISSN] 0172-780X

[Journal-full-title] Neuro endocrinology letters

[ISO-abbreviation] Neuro Endocrinol. Lett.

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] Sweden

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] APC germ-line allele-specific expression in familial adenomatous polyposis.

: e22037 Background: About 13% of Familial Adenomatous Polyposis (FAP) families and 70% of Attenuated FAP families remain with unknown molecular pathogenic cause after APC and MYH mutational analyses.

The aim of the study was to determine the presence of germline ASE in the APC gene in FAP and AFP with and without detectable APC or MYH mutations.

METHODS: Germline RNA from fresh frozen and/or cultured lymphocytes of 17 APC/MYH-negative Polyposis (7 FAP, 10 AFAP) families (21 individuals) and 35 APC-mutated Polyposis (30 FAP, 5 AFAP) families (60 individuals) was analyzed.

ASE was investigated by single nucleotide primer extension (SNuPE) of rs2229992 APC coding SNP.

We found that 17% (3 of 17) APC/MYH(-) FAP and AFAP families showed ASE (range=1.17-1.39) and ASE co-segregated with disease.

Eleven of 35 (31%) APC-FAP/AFAP harbored ASE (range=1.20-7.76), and the mutant allele was underexpressed in each case.

CONCLUSIONS: APC ASE is present in a significant proportion (17%) of APC/MYH(-) FAP or AFAP.

ASE, due to nonsense-mediated decay (NMD), is present in APC-FAP and is associated with specific mutation location, similar to reports for other hereditary syndromes.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 27963154.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Novel de novo BRCA1 mutation in a woman with early onset breast cancer.

: e22143 Background: Germline mutations in BRCA1/2 account for a significant portion of hereditary breast/ovarian cancer.

Mutation carriers usually have a family history of breast/ovarian cancer or early onset disease.

Rarely, germline mutations are found only in the probands but not in any family members.

Such de novo mutations have been reported in diseases such as hemophilia A, thalassaemia and familial adenomatous polyposis.

De novo mutations in the BRCA1 or BRCA2 genes are rare and the few reported have been in BRCA2.

Here, we describe de novo as well as novel mutation of the BRCA1 gene in a breast cancer patient.

METHODS: Blood DNA samples from a 30 year old Chinese woman with breast cancer and no family history of cancer was tested for a BRCA1/2 mutation by full gene sequencing and Multiple Ligation-dependent Probe Amplification (MLPA).

MLPA revealed a large deletion of exons 1 to 12 of BRCA1 in the proband.

MLPA performed on 5 family members: proband's mother and father (who were 1^st degree relative- cousins), stepmother (mother's biological sister), 2 sisters (1, same parents; 1, same father and stepmother) found no similar deletion.

CONCLUSIONS: We report a novel de novo BRCA1 deletion mutation encompassing exons 1 - 12 in a Chinese breast cancer patient of early onset with no family history.

Identification of this large deletion confirms the importance of pursuing rearrangement testing if full gene sequencing fails to detect a point mutation or short insertion deletion.

The mutation found in this study is de novo.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 27963527.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

: e20569 Background: Improvement of quality of life (QOL) is a major therapeutic goal for men with advanced prostate cancer (APC).

The PROSQOLI consists of a series of 9 linear analog self-assessment (LASA) scales that evaluate pain, fatigue, appetite, constipation and other symptoms, and overall well-being; it was designed and validated for use in patients with APC.

METHODS: Consenting patients with APC completed a touch screen version of the PROSQOLI before seeing the doctor at visits to the outpatient clinic.

In phase I of the study physicians did not have access to this information; in phase II physicians were provided with results of the PROSQOLI and its changes from previous visits.

Rates of documentation did not differ between study phases.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 27961125.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Evaluation of stool melting curve analysis of methylated CpG island promoters as an alternative for early noninvasive diagnosis of colorectal tumors.

The aim of the present study was to assess the clinical usefulness of a panel of methylation biomarkers in stool DNA in the diagnosis of colorectal tumors using Methylation Curve (MC) analyses, a technique that simultaneously analyze all CpG residues within a promoter.

METHODS: Promoter methylation status of 5 tumor-related genes (RARB2, p16^INK4a, MGMT, p14^ARF and APC) was analyzed in DNA stool samples and corresponding tissues in an initial set of 12 newly diagnosed patients with primary colorectal carcinomas and 20 with colorectal adenomas using Methylation-specific PCR (MSP).

Results were validated in a set of 88 patients (20 healthy subjects, 17 inflammatory bowel disease, 23 adenomas, 28 carcinomas) using MC analyses.

Analytical sensitivity of MC was 5% of methylated alleles for p16^INK4a, p14^ARF, RARB2 and APC and 10% for MGMT.

CONCLUSIONS: Melting Curve analysis of a panel of methylation markers in stool DNA is a good alternative for the early non-invasive diagnosis of colorectal tumors.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 27964470.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] APC allele-specific expression in carriers of Ashkenazi Jewish mutation I1307K.

: e22181 Background: I1307K is a missense APC variant with incomplete penetrance that has been found in 6% of Jewish Ashkenazi population and confers a two-fold increased risk to develop multiple adenomas and colorectal tumours.

It remains unknown whether the presence of this mutation modifies APC expression.

CONCLUSIONS: I1307K variant is not associated with allelic specific expression at the germline level.

I1307K overexpression is not selected for during tumor progression.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 27963596.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Fixed dose rate infusion of gemcitabine and UFT combination chemotherapy in patients with advanced biliary cancer.

Gemcitabine and UFT combination chemotherapy showed promising results in advanced pancreatic cancer(APC) and fixed dose- rate(FDR) infusion(10mg/m²/min) of gemcitabine is more effective than 30min-infusion in APC patients.

Partial response was 24.2% and disease control rate was 51.5%.

The estimated median time to progression(TTP) was 87 days(95% CI 51-123).

Median overall survival was 243 days(95% CI 114-372).

Polymorphism of XRCC1 was related to TTP(TTP of wild, heterozygous variant and homozygous variant type was 162, 71 and 25 days, respectively. p=0.0039).

QOL as a secondary endpoint was not analyzed at this time.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 27962362.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

: 10519 Background: Aggressive fibromatosis (AF) or desmoid tumors are monoclonal proliferations which are locally invasive but do not metastasise.

Sporadic tumors are usually associated with mutations in the beta-catenin gene CTNNB1whereas those occurring in the context of familial adenomatous polyposis usually have inactivating mutations in APC.

When surgery and radiotherapy are not applicable or fail to control the disease, systemic treatment with anti-oestrogens, non steroidal anti-inflammatory drugs (NSAIDs) and chemotherapy can be used.

RESULTS: The female/male ratio was 9:1 and the median age at presentation was 39.5 years (range 18-53).

Objective response according to RECIST was achieved in 4/10 patients and in 5 patients the best response was stable disease.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 27963658.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

: 4504 Background: Single-agent gemcitabine (G) remains standard treatment for advanced pancreatic adenocarcinoma (APC).

In Arm B, P 25 mg/m2 weekly (with the exception of day 22) was added to G, same dose used in Arm A (Colucci et al, Cancer 2002; 94:902-10).

After a median follow-up of 38.2 months and 357 deaths, median OS was 8.3 vs 7.2 months in arm A and B, respectively (HR 1.10, 95% CI 0.89-1.35, p=0.38).

Median PFS was 3.9 vs 3.8 months in arm A and B, respectively (HR 0.97, 95% CI 0.80-1.19, p=0.80).

ORR was 10.1% in arm A and 12.9% in B (p=0.37).

CONCLUSIONS: Weekly combination of P and G, compared to single-agent G as 1st-line treatment of APC, failed to demonstrate any improvement in OS, PFS, ORR and clinical benefit.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 27962688.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

The investigational ProCaM assay detects CpG island methylation within the promoter regions of three markers (GSTP1, RARß2, and APC) that are indicative of the presence of prostate cancer.

METHODS: Assay reproducibility: 8 operators from 4 external clinical laboratories tested a panel comprised of a negative panel member (NM2C5 cells) for the internal control (ß-Actin), a high positive and low positive panel members (LNCaP cells) for all 3 markers and ß-Actin.

The overall intersite %CV and SD values for Cts were = 9.2% and 1.49%, respectively.

The percent agreement with qualitative (positive/negative) outcome for High, Low, and Negative panel members was = 98% for GSTP1, RARß2, APC, and ß-Actin.

Using the result categories of negative and positive with identical cutoffs for GSTP1, RARß2, APC for samples with >5 ssDNA copies 98% concordance was observed for all 3 lots evaluated.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 27963156.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] A phase II study of capecitabine (CAP) plus PHY906 in patients (pts) with advanced pancreatic cancer (APC).

: e15508 Background: Gemcitabine (G) is regarded as the standard treatment for pts with APC.

Therefore, 1500mg/m² of CAP and PHY906 was further tested in a phase II study as second-line treatment in pts with APC.

METHODS: Pts with G-refractory APC with ECOG PS <2 were treated with CAP 1500mg/m² d1-7 with PHY906 800mg d1-4 q 2 wks.

There were 7 deaths on/within 30 days of study treatment, 6 related to PD and 1 had acute MI.

CONCLUSIONS: This is the first clinical study to evaluate a botanical formulation PHY906 with CAP in G-refractory APC pts.

CAP + PHY906 regimen appears a safe and feasible salvage therapy in APC and warrants further investigation.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 27962238.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Effect of the I1307K polymorphism in APC confers a higher risk for polyp recurrence in Jewish Ashkenazi carriers.

: e22003 Background: The I1307K adenomatous polyposis coli gene variant, prevalent among Ashkenazi Jews, may increase risk for colorectal neoplasia [colorectal cancer (CRC) and CR adenoma].

Germline genetic analysis for the APC I1307K variant was performed using real-time PCR for DNA extracted from peripheral mononuclear cells.

Among Ashkenazi Jews, the I1307K variant was significantly more prevalent among persons with a personal or family history (1^st degree) of CR neoplasia (p=0.01) as compared to Ashkenazi Jews with no family history.

The histopathological features of adenomas and cancers did not differ between carriers and non-carriers.

CONCLUSIONS: In the general population, the APC I1307K variant does not change the risk or prognosis of colorectal neoplasia in carriers and does not necessarily change their clinical practice.

Nevertheless, the variant, which is more prevalent among high risk individuals of Ashkenazi Jewish origin, is an important risk factor for the assessment of recurrence of neoplasia as it confers a higher risk for polyp recurrence in this population.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 27963171.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

: e11505 Background: We have previously shown that alkylating agent based chemotherapy regimens (AQT) could induce MIS in the PBMNF of BC patients in parallel to a decrease in the expression of the protein hMSH2 in these cells (Fonseca et al., 2005, Breast Cancer Res, 7, R28-32).

Blood (pfDNA and PBMNNF) and urine (ufDNA) were evaluated at time 0,3 and 6 months with 6 MIS markers (BAT40,BAT26, MR2,TP53 PCR15.1, APC and ALU).

We incubated in vitro cultures of MCF- 7 cells and PBMNF cells with M at a dose of 0.7μg/ml for 30 minutes with and without A at 20% of the M dose and evaluated serially for 48 hours for MIS and hMH2 expression by immunohistochemistry.

Interestingly, fpDNA levels increased significantly in patients with measurable disease who responded to therapy (47.4 ± 13.34 vs 14.37± 5.32; p = 0.021).

CONCLUSIONS: We conclude that Chemotherapy as well as Fulvestran can induce MIS in normal and malignant cells and that in vitro these effects could be reproduced by treatment with M and prevented in normal cells by A.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 27964585.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Various pathogenesis have been given for the adenocarcinoma, like mutation in the E-catherin gene, amplification of COX-2, HGF/ SF, VEGF; deletion of FHIT, APC, p53 but none have provided a definite target for treatment.

52.63 % of the non-mucinous type of gastric adenocarcinoma showed positive p53 immunoreactivity.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 27962795.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Recently, we showed that triplet chemotherapy consisting of gemcitabine 800 mg/m² (10 mg/m²/min) followed by oxaliplatin 85 mg/m² and 48-hour infusion of 5-FU/LV 3,000 and 150 mg/m² Q 2 weeks, the GOFL regimen, is feasible and active for pts with APC.

Patients who did not experience disease progression (PD) after 6 cycles of GOFL would had CCRT consisting of weekly gemcitabine 400mg/m² plus 50.4Gy/28 fractions of radiation 4-6 weeks later.

After CCRT, pts were re-evaluated for surgical intervention and those with unresectable disease would continue GOFL until PD, unacceptable toxicity, patient's refusal or death.

Among the 34 (68%) with objective response or stable disease after 6 cycles of ICT, 27 (54%) who completed the assigned multimodality treatment are categorized as CCRT group; whiles 7 (14%) who either declined CCRT (in 5) or still on ICT (in 2) are categorized as non-CCRT group.

The median PFS and OS for the ITT population were 9.1 and 14.5 months, respectively.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 27962329.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Vaccine-induced immunity against the HER2 ICD correlates with antitumor responses in animal models.

DNA-based vaccines offer a strategy to immunize against multiple tumor antigens and are able to elicit both CTL and T helper immune responses.

However, DNA vaccines have been poorly immunogenic due in part to inefficient APC transfection.

Vaccine site biopsies were analyzed for plasmid persistence via RT-PCR, 1 and 6 months after vaccination.

13/21 (62%) subjects in Arm 1 developed T-cell immunity, defined as HER2-specific T cell precursors:PBMC, to the HER2 protein (median 1:5,972, range 1:717-1:3,000,000) and to p776, a HER2 pan DR binding epitope (median 1:3,150, range 1:543-1:108,696).

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 27961998.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] The clinical pathogensis significance associated with mutation of APC MCR in colorectal neoplasms.

: e15119 Background: To explore the clinical pathogensis evalution of codon 1493,1367 and 1328 mutations in MCR (mutation cluster region) of exon 15 of APC (Adenomatous polyposis coli) gene in cases of colorectal neoplasm and the family history.

METHODS: The specimens from 21 colorectal adenoma specimens groups,16 colorectal carcinoma groups, 20 healthy germline groups with positive familial history and 8 healthy germline groups without familial history.

MCR of APC gene were extracted and specificly amplified, then sequenced by sequencer, the codon mutations were analyzed between the 4 groups and various genotypes tested with Chi-square.

The allele mutations were checked out four genotypes such as 4478(G→A), 41/69(59.4%); 4478(G/A), 22/69(31.9%); 4096(C/T), 1/69 (1.4%) and 3979(C/T), 5/69(7.2%); but the significant groups status (P<0.05) were shown between the adenoma and nonfamily history group on the analysis of 4478(G→A) and (G/A), also the significant differences were tested between the with and without family history on the analysis of 4478(G→A).

The significant differences (P<0.05) in pathogensis mutant phenotypes were involved between 4478(G→A) with 4478(G/A), 4096(C/T) and 3979(C/T), respectively; also showed between 4478(G/A) with 4096(C/T) and 3979(C/T); but not between 4096(C/T) and 3979(C/T) (P>0.05).

CONCLUSIONS: In our data, the highest mutant frequency 4478(G→A) of 1493(ACG>ACA) presented to the significant phenotype of positive history and adenoma, but 4478 (G/A) were associated with colorectal adenocancer, which was discovered in the different effect to candidators despite the same synonymous mutation.

In researches, APC MCR codon 1367 and 1328 genotyping were significantly presented in the colorectal cancergenetic phenotypes in somatic cells only.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 27960846.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

The identification of circulating tumor cells (CTCs) in the blood of cancer patients, based on their aberrant methylation profile, appears as a potential tool for early detection and provides therefore the promise of a non-invasive and affordable cancer detection test.

The more frequently aberrant methylated genes were: rassf1A promoter (62.5%), esr1 (54.17%), apc (54.17%) and rassf1A exon 1 (50%).

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 27963494.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

: e20595 Background: 15.4% of pts with GI cancers treated with CAP alone at 1250mg/m² BID D1-14 q 3 wks (14/7) develop G3/4 diarrhea (Hoff et al. JCO, 2001).

METHODS: We prospectively evaluated 44 pts treated on a clinical study with CAP plus PHY906 for diarrhea (experimental arm) and compared to historical data by Hoff et al., CAP 14/7 alone arm (control arm).

Experimental arm consisted of pts with refractory solid tumors in phase I and gemcitabine-refractory advanced pancreatic cancer (APC) in phase II.

Ph II treated pts with APC at 1500 mg/m² and PHY906 800mg BID D1-4.

Phase I pts had GI malignancies; 15 (63%) had APC and 6 (25%) colorectal.

One pt with APC who received 3 cycles at the 1500mg/m² dose level was diarrhea-free until he was removed from the study; he continued on single-agent CAP at 1000mg/m² BID and developed G3 diarrhea.

As an underlying mechanism of CID may include cytokine activation, evalation of cytokines is ongoing.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 27961165.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Some familial GI cancer experts have recommended that younger patients with curable CRC undergo definitive subtotal colectomy at initial presentation.

Type of resection was classified as complete (total/subtotal colectomy, proctocolectomy) or segmental.

The young patients had significantly higher rates of identifiable risk factors for CRC (IBD, FAP/HNPCC, family history of cancer) and were significantly more likely to undergo complete resection (23.38% vs 6.01%, OR 4.78).

Factors contributing to complete resection were site of disease (colon), IBD, and family history of CRC (Table).

Four patients (2.6%) who underwent segmental resection developed metachronous disease at a median of 66.38 months post resection.

Overall survival was not influenced by extent of resection.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 27964525.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Wnt signaling somatic alterations in apc-associated fap adenomas.

: e22046 Background: APC mutations are believed to constitutively activate the wnt pathway in colorectal tumors.

Our goal was to comprehensively characterize Wnt signaling components in a set of APC-associated FAP tumors both at the DNA and RNA levels.

METHODS: Sixty adenomas from FAP cases harboring pathogenic APC mutations were included (10 adenomas and 1 normal mucosa per case).

Somatic APC and KRAS alterations, β-catenin immunostaining and qRT-PCR of APC, MYC, AXIN2 and SFRP1 were analyzed. aCGH was also assessed in 26 FAP adenomas and 24 additional paired normal-adenoma-carcinoma samples.

RESULTS: A second APC alteration was present in 30 (50%) of adenomas (26 LOH and 4 point mutations).

LOH was only occasionally associated with loss of genetic material.

In 3 of 6 cases APC mRNA was overexpressed in macroscopically normal mucosa.

In these cases diminished APC levels mRNA were observed in 11 of 30 adenomas analyzed..

In the remaining 3 cases APC mRNA was already underexpressed in normal mucosa with only 3 of 30 adenomas showing further underexpression.

In FAP normal mucosae MYC was overexpressed (logratio range: 3.37-5.66).

All adenomas showed further MYC (logratio range: 1.78-2.92) and AXIN2 overexpression (logratio range: 1.62-4.65), corregulating with APC mRNA levels (r=0.31 for MYC; r=0.59 for AXIN2).

DNA changes were more often detected in areas containing wnt genes when FAP and sporadic tumors were jointly analyzed (p=0.02).

CONCLUSIONS: Wnt pathway is altered, at the DNA and/or RNA level, in all APC mutant FAP tumors.

MYC overexpression is a universal event that correlates with APC and AXIN2 expression levels as well as bcatenin nuclear accumulation.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 27963228.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Phase I clinical results of an APC-targeted hCGβ vaccine (CDX-1307) with TLR agonists.

The CDX-1307 vaccine is composed of B11 fused with hCGβ, a tumor antigen correlated with advanced stage of disease and poor prognosis in a number of common epithelial cancers, but reported at variable rates of expression.

To date, a significant mixed response was seen in one patient with pancreatic cancer (id), while stable disease has been seen in 4 patients (2 with breast cancer = 25, 27 weeks and 2 with colorectal cancer = 9+ weeks).

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 27962048.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] A prospective, randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC): Results of the CONKO 004 trial.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 27960826.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

: 4622 Background: To evaluate the benefits of adjuvant intra-operative radiation therapy after curative resection in advanced pancreatic cancer (APC) patients, a multi-center phase III trial was conducted by 11 participating institutions in Japan.

METHODS: Eligibility included pts with potentially resectable APC (duct cell origin) by image diagnosis.

Patients were randomized in a 1:1 ratio to adjuvant IORT or surgery alone less than a week before surgery.

The radiation field included the tumor bed and in most cases included the celiac axis, superior mesenteric artery, and the portal vein.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 27964217.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

We prospectively evaluated the effect of acquired (i.e. age, chemotherapy, tumor hystotype, history of thrombosis, body mass index and smoke) and inherited risk factors (i.e. antithrombin, protein C, protein S, homocysteine, activated protein C [APC] resistance, factor V Leiden [FVL] and Prothrombin [PT] mutations).

At multivariate analysis thrombocytosis (HR 2.8; 95% CI, 1.13-7.30, P< 0.026) and a previous episode of thrombosis (HR 12.4; 95% CI, 2.48-62.6, P< 0.0026) were significantly associated to the development of VTE .

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 27963660.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

: 2502 Background: The proton pump inhibitor omeprazole (Losec) is one of the most extensively prescribed medications worldwide and within its class, omeprazole is most frequently associated with drug interactions.

Plasma samples were obtained up to 55 hours after infusion and analyzed for irinotecan, and its metabolites SN-38, SN-38 glucuronide (SN-38G), NPC, and APC by reversed-phase high-performance liquid chromatography with fluorescence detection.

RESULTS: The mean AUCs of irinotecan and all metabolites were not significantly different between both courses (p>.151; see table).

The nadir ANC and WBC and the percentage decrease in ANC and WBC from baseline were not different between both courses (p>.529).

CONCLUSIONS: Omeprazole 40 mg did not alter the pharmacokinetics and toxicities of irinotecan.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 27961961.001).

[ISSN] 1527-7755

[Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology

[ISO-abbreviation] J. Clin. Oncol.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Recruitment of adenomatous polyposis coli and beta-catenin to axin-puncta.

The adenomatous polyposis coli (APC) tumour suppressor is a multifunctional protein involved in the regulation of Wnt signalling and cytoskeletal dynamics.

Little is known about how APC controls these disparate functions.

In this study, we have used APC- and axin-fluorescent fusion proteins to examine the interactions between these proteins and show that the functionally distinct populations of APC are also spatially separate.

Axin-RFP recruits beta-catenin destruction complex proteins, including APC, beta-catenin, glycogen synthase kinase-3-beta (GSK3-beta) and casein kinase-1-alpha (CK1-alpha).

Recruitment into axin-RFP puncta sequesters APC from clusters at cell extensions and this prevents its microtubule-associated functions.

The interaction between APC-GFP and axin-RFP within the cytoplasmic puncta is direct and dramatically alters the dynamic properties of APC-GFP.

However, recruitment of APC to axin puncta is not absolutely required for beta-catenin degradation.

An axinDeltaDIX mutant did not form puncta, but still mediated recruitment of destruction complex proteins and phosphorylation of beta-catenin.

We conclude that there are distinct pools of APC and that the formation of axin puncta, rather than the axin/APC complex, is essential for beta-catenin destruction.

[MeSH-major] Adenomatous Polyposis Coli Protein / metabolism. Repressor Proteins / metabolism. beta Catenin / metabolism

[MeSH-minor] Animals. Axin Protein. Cell Line. Cytoplasm / metabolism. Cytoplasm / ultrastructure. Dogs. Fluorescence Resonance Energy Transfer. Green Fluorescent Proteins / genetics. Green Fluorescent Proteins / metabolism. Humans. Mice. Recombinant Fusion Proteins / genetics. Recombinant Fusion Proteins / metabolism

Genetic Alliance. consumer health - Familial Adenomatous Polyposis (FAP).

COS Scholar Universe. author profiles.

NCI CPTC Antibody Characterization Program. NCI CPTC Antibody Characterization Program .

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 18591934.001).

[ISSN] 1476-5594

[Journal-full-title] Oncogene

[ISO-abbreviation] Oncogene

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] England

[Chemical-registry-number] 0 / Adenomatous Polyposis Coli Protein; 0 / Axin Protein; 0 / Recombinant Fusion Proteins; 0 / Repressor Proteins; 0 / beta Catenin; 147336-22-9 / Green Fluorescent Proteins

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Phenotypes of invasion in sporadic colorectal carcinomas related to aberrations of the adenomatous polyposis coli (APC ) gene.

AIMS: To determine whether the dissociation of tumour cells from neoplastic glands in colorectal carcinomas is caused by disruption of the wnt-signalling pathway and whether the adenomatous polyposis coli (APC) protein is implicated in this.

METHODS AND RESULTS: In a series of 99 clinically sporadic colorectal carcinomas, APC exon 15 mutations, loss of heterozygosity (LOH) and promoter methylation were found in 49, 20 and 23 cases, respectively.

Singly, these APC aberrations were not associated with the degree of tumour cell dissociation, but dissociation was higher for the cases with combined APC mutation and LOH.

Immunohistochemical beta-catenin translocation to the nucleus correlated with APC aberrations.

Tumour growth pattern (expansive/infiltrative/diffuse) and tumour stroma (desmoplastic common-type versus keloid-like) showed a statistically significant association with tumour cell dissociation and with beta-catenin translocation.

Of other molecular alterations tested (p53 mutation; LOH at 17p13, 18q, 9p21; CpG island methylator phenotype), only the highly microsatellite unstable status (n = 11) was negatively associated.

CONCLUSIONS: In colorectal carcinomas, wnt dysregulation relates to APC aberrations, but wnt dysregulation and APC aberrations are not strictly required for tumour cell dissociation, and additional and/or alternative factors must play a role.

[MeSH-major] Adenocarcinoma, Mucinous / genetics. Colorectal Neoplasms / genetics. Genes, APC. Loss of Heterozygosity / genetics. Mutation

[MeSH-minor] Adult. Aged. Aged, 80 and over. Biomarkers, Tumor / metabolism. Cadherins / metabolism. Cell Nucleus / metabolism. Cell Nucleus / pathology. Female. Humans. Male. Microsatellite Instability. Middle Aged. Neoplasm Invasiveness. Neoplasm Staging. Phenotype. Translocation, Genetic. Wnt Proteins / genetics. Wnt Proteins / metabolism. beta Catenin / metabolism

Genetic Alliance. consumer health - Familial Adenomatous Polyposis (FAP).

MedlinePlus Health Information. consumer health - Colorectal Cancer.

COS Scholar Universe. author profiles.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 17257127.001).

[ISSN] 0309-0167

[Journal-full-title] Histopathology

[ISO-abbreviation] Histopathology

[Language] eng

[Publication-type] Journal Article

[Publication-country] England

[Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Cadherins; 0 / Wnt Proteins; 0 / beta Catenin

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Involvement of adenomatous polyposis coli (APC) gene in testicular yolk sac tumor of infants.

On the other hand, recent epigenetic studies suggest the involvement of some tumor suppressor genes, including the adenomatous polyposis coli (APC) gene.

In the present study, we examined 10 infantile pure YSTs for mutation, allelic loss, promoter methylation, and protein expression status of the APC gene to evaluate whether the APC gene plays a significant role in the pathogenesis of infantile YSTs.

Loss of heterozygosity at 5q21, where the APC gene is localized, was detected in at least 3 (30%) of the 9 YSTs examined.

Immunohistochemically, 8 infantile YSTs did not express the APC protein, whereas 2 YSTs without showing APC methylation, as well as germ cells of normal infantile testes, expressed this protein in the cytoplasm.

These data indicate that inactivation of the APC gene, by allelic loss and/or promoter methylation, is related to the occurrence of infantile YSTs.

[MeSH-major] Adenomatous Polyposis Coli Protein / genetics. Endodermal Sinus Tumor / genetics. Genes, APC. Loss of Heterozygosity. Testicular Neoplasms / genetics

Genetic Alliance. consumer health - Familial Adenomatous Polyposis (FAP).

Genetic Alliance. consumer health - Yolk sac tumor.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 16360415.001).

[ISSN] 0046-8177

[Journal-full-title] Human pathology

[ISO-abbreviation] Hum. Pathol.

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] United States

[Chemical-registry-number] 0 / Adenomatous Polyposis Coli Protein; 0 / Biomarkers, Tumor

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Functional definition of the mutation cluster region of adenomatous polyposis coli in colorectal tumours.

The mutation cluster region (MCR) of adenomatous polyposis coli (APC) is located within the central part of the open reading frame, overlapping with the region encoding the 20 amino acid repeats (20R) that are beta-catenin-binding sites.

Each mutation in the MCR leads to the synthesis of a truncated APC product expressed in a colorectal tumour.

The MCR extends from the 3' border of the first 20R coding region to approximately the middle of the third 20R coding region, reflecting both positive and negative selections of the N- and C-terminal halves of the APC protein in colon cancer cells, respectively.

In contrast, the second 20R escapes selection and can be either included or excluded from the truncated APC products found in colon cancer cells.

To specify the functional outcome of the selection of the mutations, we investigated the beta-catenin binding capacity of the first three 20R in N-terminal APC fragments.

Similarly, we also show that the tumour-associated truncations abolish the interaction of beta-catenin with the third 20R.

Thus, our data provide a functional definition of the MCR: the APC fragments typical of colon cancer are selected for the presence of a single functional 20R, the first one, and are therefore equivalent relative to beta-catenin binding.

[MeSH-major] Adenomatous Polyposis Coli Protein / chemistry. Adenomatous Polyposis Coli Protein / metabolism. Colonic Neoplasms / genetics. Sequence Deletion. beta Catenin / metabolism

[MeSH-minor] Amino Acid Sequence. Bacterial Proteins / genetics. Bacterial Proteins / metabolism. Cell Line, Tumor. Humans. Luminescent Proteins / genetics. Luminescent Proteins / metabolism. Multigene Family. Protein Binding. Recombinant Fusion Proteins / chemistry. Recombinant Fusion Proteins / genetics. Recombinant Fusion Proteins / metabolism. Repetitive Sequences, Amino Acid

Genetic Alliance. consumer health - Familial Adenomatous Polyposis (FAP).

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 18387968.001).

[ISSN] 1460-2083

[Journal-full-title] Human molecular genetics

[ISO-abbreviation] Hum. Mol. Genet.

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] England

[Chemical-registry-number] 0 / Adenomatous Polyposis Coli Protein; 0 / Bacterial Proteins; 0 / Luminescent Proteins; 0 / Recombinant Fusion Proteins; 0 / beta Catenin; 0 / yellow fluorescent protein, Bacteria

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] DHPLC analysis of adenomatous polyposis coli (APC) mutations using ready-to-use APC plates: simple detection of multiple base pair deletion mutations.

The adenomatous polyposis coli (APC), which is the susceptible gene for familial adenomatous polyposis (FAP) and sporadic colorectal cancer, spans 15 exons.

The open reading frame of APC is 8529 bp, which encodes 2843 amino acids.

Thus, we developed a novel APC ready-to-use plate for high-throughput mutational analysis by denaturing high performance liquid chromatography (DHPLC).

To prepare the ready-to-use APC plate, all 38 primer pairs and PCR mixtures were aliquoted into individual wells of a 96-well plate, and frozen at -20 degrees C until use.

We examined a total of 27 FAP patient samples with APC germline mutations (17 for multiple bp deletions, 1 for 1 bp deletion, 9 for nonsense mutations) and 50 APC-negative noncarriers.

All 17 multiple bp deletion mutations were detected during the initial 50 degrees C running analysis and thus ruled out for further analyses.

More than 50% of the APC germline mutations were multiple base pair deletions and efficiently selected by omitting time-consuming partial denaturing conditions.

[MeSH-major] Adenomatous Polyposis Coli / genetics. Adenomatous Polyposis Coli Protein / genetics. Base Pairing / genetics. Chromatography, High Pressure Liquid / methods. Gene Deletion. Mutation

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 18554166.001).

[ISSN] 1090-6576

[Journal-full-title] Genetic testing

[ISO-abbreviation] Genet. Test.

[Language] eng

[Publication-type] Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] United States

[Chemical-registry-number] 0 / Adenomatous Polyposis Coli Protein

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] [Methylation status and protein expression of adenomatous polyposis coli (APC) gene in breast cancer].

BACKGROUND & OBJECTIVE: Protein expression product of adenomatous polyposis coli (APC) gene is an important component of Wnt signal transduction pathway.

APC gene inactivation leads to dysfunction of beta-catenin protein degradation, and then activates Tcf/Lef and causes abnormal transcription of oncogenes, such as c-myc, c-jun and cyclin D1, finally leads to carcinogenesis.

This study was to investigate the correlation of methylation status of APC gene promoter 1A to protein expression of APC gene in breast cancer, and analyze the correlation of aberrant methylation of APC gene to clinicopathologic features of breast cancer.

METHODS: Methylation status of APC gene promoter 1A in 76 specimens of breast cancer and corresponding adjacent tissues was detected by methylation-specific polymerase chain reaction; the expression of APC protein was detected by immunohistochemistry.

RESULTS: The methylation rate of APC gene promoter 1A was significantly higher in breast cancer than in pericancerous normal breast tissue (36.8% vs. 0, P < 0.05).

The positive rate of APC protein was significantly lower in breast cancer than in normal breast tissue (52.4% vs. 100%, P < 0.05).

The promoter methylation of APC gene was positively correlated to TNM stage (r=0.296, P < 0.05), but negatively correlated to the expression of APC protein (r=-0.368, P < 0.05).

CONCLUSION: Abnormal methylation of APC gene occurs in the progression of breast cancer, which is the main cause for the absence of APC protein expression, and the major mechanism of inactivation of APC gene.

[MeSH-major] Adenomatous Polyposis Coli Protein / metabolism. Breast Neoplasms / genetics. Breast Neoplasms / metabolism. DNA Methylation. Genes, APC

Genetic Alliance. consumer health - Familial Adenomatous Polyposis (FAP).

Genetic Alliance. consumer health - Breast Cancer.

MedlinePlus Health Information. consumer health - Breast Cancer.

NCI CPTAC Assay Portal. NCI CPTAC Assay Portal .

NCI CPTC Antibody Characterization Program. NCI CPTC Antibody Characterization Program .

NCI CPTC Antibody Characterization Program. NCI CPTC Antibody Characterization Program .

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 17562262.001).

[Journal-full-title] Ai zheng = Aizheng = Chinese journal of cancer

[ISO-abbreviation] Ai Zheng

[Language] chi

[Publication-type] English Abstract; Journal Article

[Publication-country] China

[Chemical-registry-number] 0 / Adenomatous Polyposis Coli Protein

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Prognostic impact of adenomatous polyposis coli gene expression in osteosarcoma of the extremities.

PURPOSE: To evaluate the impact of adjuvant chemotherapy on the outcome of osteosarcoma of the extremities, and to identify prognostic factors using the expression of adenomatous polyposis coli (APC), cadherin and β-catenin Wnt-signalling markers.

METHODS: The clinical, demographic, anatomic and pathological factors including a detailed analysis of the immunohistochemical expression of cadherin, β-catenin and APC were retrospectively examined in 97 patients with osteosarcoma of the extremities (metastatic and non-metastatic at diagnosis), treated with surgery and/or chemotherapy from 1985 to 2000.

RESULTS: APC immunoreactivity showed a statistically significant association with age and serum alkaline phosphatase levels (p = 0.025 and p = 0.038).

For overall survival, cadherin immunoreactivity and the interaction between APC expression and response to adjuvant chemotherapy were significant (p = 0.012 and p<0.001).

CONCLUSION: Lack of expression of cadherin was a significant variable to overall and disease-free survival.

Significantly, positive APC immunoreactivity and adjuvant chemotherapy were associated with a favourable treatment response.

[MeSH-major] Adenomatous Polyposis Coli / genetics. Bone Neoplasms / genetics. Extremities. Genes, APC. Osteosarcoma / genetics

Genetic Alliance. consumer health - Familial Adenomatous Polyposis (FAP).

Genetic Alliance. consumer health - Osteosarcoma.

MedlinePlus Health Information. consumer health - Bone Cancer.

[Email] Email this result item

Email the results to the following email address:   [X] Close

[Copyright] Copyright © 2010 Elsevier Ltd. All rights reserved.

(PMID = 20594821.001).

[ISSN] 1879-0852

[Journal-full-title] European journal of cancer (Oxford, England : 1990)

[ISO-abbreviation] Eur. J. Cancer

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] England

[Chemical-registry-number] 0 / Cadherins

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Dual roles for adenomatous polyposis coli in regulating retinoic acid biosynthesis and Wnt during ocular development.

Congenital hypertrophy/hyperplasia of the retinal pigmented epithelium is an ocular lesion found in patients harboring mutations in the adenomatous polyposis coli (APC) tumor suppressor gene.

We report that Apc-deficient zebrafish display developmental abnormalities of both the lens and retina.

Injection of dominant-negative Lef reduced Wnt signaling in the lens but did not rescue retinal differentiation defects.

In contrast, treatment of apc mutants with all-trans retinoic acid rescued retinal differentiation defects but had no apparent effect on the lens.

We identified Rdh5 as a retina-specific retinol dehydrogenase controlled by APC.

Morpholino knockdown of Rdh5 phenocopied the apc mutant retinal differentiation defects and was rescued by treatment with exogenous all-trans retinoic acid.

Microarray analyses of apc mutants and Rdh5 morphants revealed a profound overlap in the transcriptional profile of these embryos.

These findings support a model wherein Apc serves a dual role in regulating Wnt and retinoic acid signaling within the eye and suggest retinoic acid deficiency as an explanation for APC mutation-associated retinal defects such as congenital hypertrophy/hyperplasia of the retinal pigmented epithelium.

[MeSH-major] Adenomatous Polyposis Coli Protein / metabolism. Eye / embryology. Tretinoin / metabolism. Wnt Proteins / metabolism. Zebrafish / embryology

MedlinePlus Health Information. consumer health - Eye Care.

COS Scholar Universe. author profiles.

Gene Ontology. gene/protein/disease-specific - Gene Ontology annotations from this paper .

Hazardous Substances Data Bank. ALL-TRANS-RETINOIC ACID .

SciCrunch. OMIM: Data: Gene Annotation .

The Lens. Cited by Patents in .

[Email] Email this result item

Email the results to the following email address:   [X] Close

[Cites] Nat Rev Cancer. 2001 Oct;1(1):55-67 [11900252.001]

[Cites] Cancer Res. 1994 Jul 15;54(14):3676-81 [8033083.001]

[Cites] Development. 2003 May;130(10):2173-86 [12668631.001]

[Cites] Dev Biol. 2003 Jul 1;259(1):48-61 [12812787.001]

[Cites] Dev Dyn. 2003 Jul;227(3):323-34 [12815618.001]

[Cites] Gene Expr Patterns. 2003 Oct;3(5):659-62 [12972002.001]

[Cites] Nature. 2003 Oct 9;425(6958):633-7 [14534590.001]

[Cites] Am J Pathol. 2004 Feb;164(2):701-10 [14742273.001]

[Cites] Bull Soc Belge Ophtalmol. 2004;(292):59-64 [15253492.001]

[Cites] J Biol Chem. 2004 Aug 13;279(33):34397-405 [15190067.001]

[Cites] Am J Hum Genet. 2004 Oct;75(4):639-46 [15322982.001]

[Cites] Eur J Biochem. 2000 Jul;267(14):4315-24 [10880953.001]

[Cites] Genes Dev. 2000 Aug 1;14(15):1837-51 [10921899.001]

[Cites] Curr Biol. 2001 Jan 9;11(1):44-9 [11166179.001]

[Cites] Nat Cell Biol. 2001 Mar;3(3):E67-8 [11231588.001]

[Cites] Nat Cell Biol. 2001 Apr;3(4):429-32 [11283619.001]

[Cites] Nat Cell Biol. 2001 Apr;3(4):433-8 [11283620.001]

[Cites] Nat Genet. 2001 May;28(1):53-7 [11326276.001]

[Cites] Oncogene. 2001 Aug 9;20(35):4884-90 [11521200.001]

[Cites] Dev Biol. 2002 Jan 15;241(2):229-37 [11784107.001]

[Cites] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7286-90 [8041782.001]

[Cites] Development. 1996 Jan;122(1):195-204 [8565830.001]

[Cites] J Cell Biol. 1996 Jul;134(1):165-79 [8698812.001]

[Cites] Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13298-303 [8917585.001]

[Cites] Nature. 1997 Apr 10;386(6625):623-7 [9121588.001]

[Cites] Arch Ophthalmol. 1997 May;115(5):645-50 [9152133.001]

[Cites] Invest Ophthalmol Vis Sci. 1997 Jul;38(8):1471-5 [9224274.001]

[Cites] J Neurosci. 1997 Oct 1;17(19):7441-9 [9295390.001]

[Cites] Mol Vis. 1998 Dec 2;4:26 [9841935.001]

[Cites] Cancer Res. 1999 Apr 1;59(7):1442-4 [10197610.001]

[Cites] J Biol Chem. 2004 Dec 3;279(49):51581-9 [15358764.001]

[Cites] Science. 2005 Mar 25;307(5717):1904-9 [15790842.001]

[Cites] Neuron. 2005 Jul 7;47(1):43-56 [15996547.001]

[Cites] Nat Immunol. 2005 Aug;6(8):800-9 [16025118.001]

[Cites] J Biol Chem. 2005 Aug 26;280(34):30490-5 [15967793.001]

[Cites] Dev Biol. 2005 Sep 15;285(2):477-89 [16102745.001]

[Cites] Mech Dev. 2002 Aug;116(1-2):173-6 [12128219.001]

(PMID = 16938888.001).

[ISSN] 0027-8424

[Journal-full-title] Proceedings of the National Academy of Sciences of the United States of America

[ISO-abbreviation] Proc. Natl. Acad. Sci. U.S.A.

[Language] eng

[Databank-accession-numbers] GENBANK/ DQ000308

[Grant] United States / NCI NIH HHS / CA / R01 CA116468

[Publication-type] Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

[Publication-country] United States

[Chemical-registry-number] 0 / Adenomatous Polyposis Coli Protein; 0 / Oligonucleotides, Antisense; 0 / Wnt Proteins; 5688UTC01R / Tretinoin

[Other-IDs] NLM/ PMC1569177

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Loss of adenomatous polyposis coli gene function disrupts thymic development.

Loss of the adenomatous polyposis coli (APC) protein is a common initiating event in colon cancer.

Here we show that thymocyte-specific loss of APC deregulated beta-catenin signaling and suppressed Notch-dependent transcription.

Simultaneously, the loss of APC prolonged the mitotic metaphase-to-anaphase checkpoint and impaired chromosome segregation, blocking development beyond the double-negative 4 stage.

Thus, loss of APC in immature thymocytes has consequences distinct from those of deregulation of beta-catenin signaling and is essential for T cell differentiation.

COS Scholar Universe. author profiles.

Gene Ontology. gene/protein/disease-specific - Gene Ontology annotations from this paper .

KOMP Repository. gene/protein/disease-specific - KOMP Repository (subscription/membership/fee required).

Mouse Genome Informatics (MGI). Mouse Genome Informatics (MGI) .

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 16025118.001).

[ISSN] 1529-2908

[Journal-full-title] Nature immunology

[ISO-abbreviation] Nat. Immunol.

[Language] ENG

[Grant] United States / NCI NIH HHS / CA / R01 CA104547; United States / NCI NIH HHS / CA / R01 CA104547-01A1; United States / NIAID NIH HHS / AI / R01 AI059676-02; United States / NIAID NIH HHS / AI / R01 AI059676-01; United States / NIAID NIH HHS / AI / R01 AI059676

[Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.

[Publication-country] United States

[Chemical-registry-number] 0 / Adenomatous Polyposis Coli Protein; 0 / CTNNB1 protein, mouse; 0 / Cytoskeletal Proteins; 0 / Membrane Proteins; 0 / Receptors, Antigen, T-Cell, alpha-beta; 0 / Receptors, Notch; 0 / Trans-Activators; 0 / beta Catenin; EC 2.7.7.- / VDJ Recombinases

[Other-IDs] NLM/ NIHMS33757; NLM/ PMC4662936

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Systematic peptide array-based delineation of the differential beta-catenin interaction with Tcf4, E-cadherin, and adenomatous polyposis coli.

Nuclear accumulation of the complex between beta-catenin and proteins of the T-cell factor (Tcf) family is a hallmark of many cancers.

Targeting this interaction for drug development is complicated by the fact that E-cadherin and adenomatous polyposis coli (APC) bind to overlapping sites on beta-catenin.

To identify selective beta-catenin binding hot spots of Tcf4, E-cadherin, and APC, array technology with peptides of up to 53 amino acids length was used.

We identified minimal binding motifs in the beta-catenin ligands and showed that most of the 15-mer and 20-mer repeats of APC did not interact, at least when non-phosphorylated, and defined a consensus binding motif also present in APC.

The method allowed us to locate a hydrophobic pocket that was relevant for the Tcf, but not the E-cadherin interaction, and would thus constitute an ideal drug target site.

[MeSH-major] Cadherins / metabolism. Cytoskeletal Proteins / metabolism. DNA-Binding Proteins / metabolism. Peptides / chemical synthesis. Protein Array Analysis. Trans-Activators / metabolism. Transcription Factors / metabolism

[MeSH-minor] Animals. Binding Sites. Combinatorial Chemistry Techniques. Drug Delivery Systems. Humans. Ligands. Mice. Models, Molecular. Protein Interaction Mapping / methods. TCF Transcription Factors. Transcription Factor 7-Like 2 Protein. beta Catenin

Genetic Alliance. consumer health - Familial Adenomatous Polyposis (FAP).

NCI CPTC Antibody Characterization Program. NCI CPTC Antibody Characterization Program .

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 15591320.001).

[ISSN] 0021-9258

[Journal-full-title] The Journal of biological chemistry

[ISO-abbreviation] J. Biol. Chem.

[Language] eng

[Publication-type] Journal Article

[Publication-country] United States

[Chemical-registry-number] 0 / CTNNB1 protein, human; 0 / CTNNB1 protein, mouse; 0 / Cadherins; 0 / Cytoskeletal Proteins; 0 / DNA-Binding Proteins; 0 / Ligands; 0 / Peptides; 0 / TCF Transcription Factors; 0 / TCF7L2 protein, human; 0 / Tcf7l2 protein, mouse; 0 / Trans-Activators; 0 / Transcription Factor 7-Like 2 Protein; 0 / Transcription Factors; 0 / beta Catenin

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Aberrant methylation of the Adenomatous Polyposis Coli (APC) gene promoter is associated with the inflammatory breast cancer phenotype.

Aberrant methylation of the adenomatous polyposis coli (APC) gene promoter occurs in about 40% of breast tumours and has been correlated with reduced APC protein levels.

To what extent epigenetic alterations of the APC gene may differ according to specific breast cancer phenotypes, remains to be elucidated.

Our aim was to explore the role of APC methylation in the inflammatory breast cancer (IBC) phenotype.

The status of APC gene promoter hypermethylation was investigated in DNA from normal breast tissues, IBC and non-IBC by both conventional and real-time quantitative methylation-specific PCR (MSP).

APC methylation levels were compared with APC mRNA and protein levels.

Hypermethylation of the APC gene promoter was present in 71% of IBC samples (n=21) and 43% of non-IBC samples (n=30) by conventional MSP (P=0.047).

The APC gene also showed an increased frequency of high methylation levels in IBC (in 74% of cases, n=19) vs non-IBC (in 46% of cases, n=35) using a qMSP assay (P=0.048).

We observed no significant association between APC methylation levels by qMSP and APC mRNA or protein expression levels.

In conclusion, for the first time, we report the association of aberrant methylation of the APC gene promoter with the IBC phenotype, which might be of biological and clinical importance.

[MeSH-major] Breast Neoplasms / genetics. DNA Methylation. Genes, APC

Genetic Alliance. consumer health - Familial Adenomatous Polyposis (FAP).

Genetic Alliance. consumer health - Inflammatory breast cancer.

Genetic Alliance. consumer health - Breast Cancer.

[Email] Email this result item

Email the results to the following email address:   [X] Close

[Cites] Cancer Res. 2004 Dec 1;64(23):8558-65 [15574762.001]

[Cites] Rev Med Chil. 2004 Sep;132(9):1069-77 [15543763.001]

[Cites] Nat Rev Cancer. 2005 Mar;5(3):223-31 [15719030.001]

[Cites] Breast Cancer Res. 2005;7(2):52-8 [15743511.001]

[Cites] Breast Cancer Res Treat. 2005 Oct;93(3):237-46 [16172796.001]

[Cites] J Mol Diagn. 2006 May;8(2):209-17 [16645207.001]

[Cites] Curr Opin Oncol. 2006 Nov;18(6):563-71 [16988576.001]

[Cites] Clin Cancer Res. 2006 Nov 15;12(22):6626-36 [17121881.001]

[Cites] Nucleic Acids Res. 2000 Apr 15;28(8):E32 [10734209.001]

[Cites] Eur J Cancer. 2000 Jan;36(2):242-8 [10741284.001]

[Cites] Curr Top Microbiol Immunol. 2000;249:101-18 [10802941.001]

[Cites] Blood. 2000 May 1;95(9):2997-9 [10841615.001]

[Cites] Am J Pathol. 2000 Jun;156(6):1997-2005 [10854222.001]

[Cites] Carcinogenesis. 2000 Jul;21(7):1453-6 [10874025.001]

[Cites] Cancer Res. 2000 Aug 15;60(16):4366-71 [10969779.001]

[Cites] Cancer Res. 2000 Nov 1;60(21):5954-8 [11085511.001]

[Cites] Hum Mol Genet. 2001 Apr;10(7):721-33 [11257105.001]

[Cites] Ai Zheng. 2007 Jun;26(6):586-90 [17562262.001]

[Cites] Zhonghua Yu Fang Yi Xue Za Zhi. 2007 Jun;41 Suppl:17-9 [17767851.001]

[Cites] Br J Cancer. 2007 Oct 22;97(8):1165-74 [17848951.001]

[Cites] Science. 1991 Aug 9;253(5020):665-9 [1651563.001]

[Cites] Br J Cancer. 2001 Jul 6;85(1):69-73 [11437404.001]

[Cites] Clin Cancer Res. 2001 Jul;7(7):1998-2004 [11448917.001]

[Cites] Cancer Res. 2002 Jan 15;62(2):371-5 [11809682.001]

[Cites] Methods. 2001 Dec;25(4):402-8 [11846609.001]

[Cites] Oncogene. 2002 Aug 12;21(35):5388-93 [12154401.001]

[Cites] J Clin Oncol. 2002 Sep 1;20(17):3628-36 [12202663.001]

[Cites] Carcinogenesis. 2003 Feb;24(2):193-8 [12584167.001]

[Cites] Cancer Res. 2003 Nov 15;63(22):7641-5 [14633683.001]

[Cites] Ann N Y Acad Sci. 2004 Jun;1022:44-9 [15251938.001]

[Cites] Blood. 2004 Sep 1;104(5):1586-7; author reply 1587-8 [15317735.001]

[Cites] Clin Cancer Res. 2004 Sep 15;10(18 Pt 1):6189-93 [15448006.001]

[Cites] Aust N Z J Surg. 1984 Feb;54(1):11-5 [6586161.001]

[Cites] Nature. 1987 Aug 13-19;328(6131):614-6 [3039373.001]

[Cites] Cell. 1990 Jun 1;61(5):759-67 [2188735.001]

[Cites] Cell. 1991 Aug 9;66(3):589-600 [1651174.001]

[Cites] Cell. 1991 Aug 9;66(3):601-13 [1678319.001]

[Cites] Science. 1991 Aug 9;253(5020):661-5 [1651562.001]

[Cites] Nature. 1992 Sep 17;359(6392):235-7 [1528264.001]

[Cites] Hum Mol Genet. 1992 Jul;1(4):229-33 [1338904.001]

[Cites] Br J Cancer. 1993 Jul;68(1):64-8 [8318422.001]

[Cites] Cancer Epidemiol Biomarkers Prev. 1994 Jun;3(4):331-3 [8061582.001]

[Cites] Science. 1996 Dec 20;274(5295):2057-9 [8953032.001]

[Cites] Cancer Res. 1998 Mar 15;58(6):1130-4 [9515795.001]

[Cites] Histopathology. 1999 Sep;35(3):249-56 [10469217.001]

[Cites] Cancer. 1953 Sep;6(5):963-8 [13094644.001]

[Cites] Br J Cancer. 1957 Sep;11(3):359-77 [13499785.001]

[Cites] Clin Cancer Res. 2004 Dec 1;10(23):7965-71 [15585631.001]

(PMID = 18841156.001).

[ISSN] 1532-1827

[Journal-full-title] British journal of cancer

[ISO-abbreviation] Br. J. Cancer

[Language] eng

[Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] England

[Other-IDs] NLM/ PMC2584952

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Association of adenomatous polyposis coli (APC) gene polymorphisms with autism spectrum disorder (ASD).

We serendipitously identified a single nucleotide polymorphism (SNP), 8636C>A (rs1804197) in the 3'-untranslated region of the adenomatous polyposis coli (APC) gene to be associated with autism spectrum disorder (ASD).

In order to gain further evidence for the association between the APC locus and ASD, we genotyped four additional adjacent common SNPs (rs2229992, rs42427, rs459552, and rs465899) in the coding regions within the APC gene in a set of Swedish ASDs and controls.

One common haplotype TGAG was found to be associated with ASD after haplotype analysis using both Haploview v3.1.1 (P = 0.006) and COCAPHASE v2.403 (P = 0.030).

This result is the first to suggest that the genomic locus at APC is associated with ASD, and that the APC gene itself is a good predisposing candidate to be evaluated in future studies due to its important role in neuronal development and function.

[MeSH-major] Autistic Disorder / genetics. Genes, APC. Genetic Linkage. Polymorphism, Single Nucleotide

Genetic Alliance. consumer health - Familial Adenomatous Polyposis (FAP).

Genetic Alliance. consumer health - Autism.

[Email] Email this result item

Email the results to the following email address:   [X] Close

[Copyright] (c) 2006 Wiley-Liss, Inc.

(PMID = 17221838.001).

[ISSN] 1552-4841

[Journal-full-title] American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics

[ISO-abbreviation] Am. J. Med. Genet. B Neuropsychiatr. Genet.

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] United States

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] The threshold level of adenomatous polyposis coli protein for mouse intestinal tumorigenesis.

The adenomatous polyposis coli (APC) gene, whose mutations are responsible for familial adenomatous polyposis, is a major negative controller of the Wnt/beta-catenin pathway.

To investigate the dose-dependent effects of APC protein in suppressing intestinal tumorigenesis, we constructed mutant mice carrying hypomorphic Apc alleles Apc(neoR) and Apc(neoF) whose expression levels were reduced to 20% and 10% of the wild type, respectively.

Although both hypomorphic heterozygotes developed intestinal polyps, tumor multiplicities were much lower than that in Apc(Delta716) mice, heterozygotes of an Apc null allele.

Like in Apc(Delta716) mice, loss of the wild-type Apc allele was confirmed for all polyps examined in the Apc(neoR) and Apc(neoF) mice.

In the embryonic stem cells homozygous for these hypomorphic Apc alleles, the level of the APC protein was inversely correlated with both the beta-catenin accumulation and beta-catenin/T-cell factor transcriptional activity.

These results suggest that the reduced APC protein level increases intestinal polyp multiplicity through quantitative stimulation of the beta-catenin/T-cell factor transcription.

We further estimated the threshold of APC protein level that forms one polyp per mouse as approximately 15% of the wild type.

[MeSH-major] Adenomatous Polyposis Coli Protein / metabolism. Genes, APC. Intestinal Neoplasms / genetics

[MeSH-minor] Alleles. Animals. Cell Transformation, Neoplastic / genetics. Cell Transformation, Neoplastic / metabolism. Cell Transformation, Neoplastic / pathology. Female. Intestinal Polyps / genetics. Intestinal Polyps / metabolism. Intestinal Polyps / pathology. Loss of Heterozygosity. Male. Mice. Mice, Inbred C57BL. Mice, Mutant Strains. beta Catenin / metabolism

KOMP Repository. gene/protein/disease-specific - KOMP Repository (subscription/membership/fee required).

Mouse Genome Informatics (MGI). Mouse Genome Informatics (MGI) .

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 16204028.001).

[ISSN] 0008-5472

[Journal-full-title] Cancer research

[ISO-abbreviation] Cancer Res.

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] United States

[Chemical-registry-number] 0 / Adenomatous Polyposis Coli Protein; 0 / beta Catenin

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Wnt-7a induces presynaptic colocalization of alpha 7-nicotinic acetylcholine receptors and adenomatous polyposis coli in hippocampal neurons.

We report here that Wnt-7a, a ligand active in the canonical Wnt signaling pathway, induces dissociation of the adenomatous polyposis coli (APC) protein from the beta-catenin cytoplasmic complex and the interaction of APC with alpha7-nAChRs in hippocampal neurons.

Interestingly, Wnt-7a induces the relocalization of APC to membranes, clustering of APC in neurites, and coclustering of APC with different, presynaptic protein markers.

Wnt-7a also increases the number and size of coclusters of alpha7-nAChRs and APC in presynaptic terminals.

Longer-term exposure to Wnt-7a increases nAChR alpha7 subunit levels in an APC-independent manner and increases clusters of alpha7-nAChRs in neurites via an APC-dependent process.

Together, these results demonstrate that stimulation through the canonical Wnt pathway regulates the presynaptic localization of APC and alpha7-nAChRs with APC serving as an intermediary in the alpha7-nAChR relocalization process.

[MeSH-major] Adenomatous Polyposis Coli Protein / metabolism. Hippocampus / metabolism. Neurons / metabolism. Presynaptic Terminals / metabolism. Proto-Oncogene Proteins / physiology. Receptors, Nicotinic / metabolism. Wnt Proteins / physiology

Genetic Alliance. consumer health - Familial Adenomatous Polyposis (FAP).

Gene Ontology. gene/protein/disease-specific - Gene Ontology annotations from this paper .

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 17507554.001).

[ISSN] 1529-2401

[Journal-full-title] The Journal of neuroscience : the official journal of the Society for Neuroscience

[ISO-abbreviation] J. Neurosci.

[Language] eng

[Grant] United States / NIDA NIH HHS / DA / DA015389; United States / NINDS NIH HHS / NS / NS040417

[Publication-type] Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

[Publication-country] United States

[Chemical-registry-number] 0 / Adenomatous Polyposis Coli Protein; 0 / Chrna7 protein, human; 0 / Chrna7 protein, mouse; 0 / Chrna7 protein, rat; 0 / Proto-Oncogene Proteins; 0 / Receptors, Nicotinic; 0 / Wnt Proteins; 0 / Wnt7a protein, mouse; 0 / Wnt7a protein, rat; 0 / alpha7 Nicotinic Acetylcholine Receptor; 0 / beta Catenin

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Ca(2+) regulates the subcellular localization of adenomatous polyposis coli tumor suppressor protein.

Microtubule (MT) plus-end tracking proteins (+TIPs) are involved in the regulation of MT plus-end dynamics and stabilization.

In the present study, the behavior of adenomatous polyposis coli (APC) following an increase in [Ca(2+)](i) was observed using Xenopus A6 epithelial cell expressing GFP-tagged APC.

An increase in [Ca(2+)](i) by cell membrane disruption or by ionomycin treatment induced dissociation of APC without depolymerizing MTs.

Inhibition of a tyrosine kinase and GSK-3beta suppressed APC dissociation upon an increase in [Ca(2+)](i).

These results suggest that Ca(2+) stimulates redistribution of APC through a tyrosine kinase- and GSK-3beta-dependent pathway.

[MeSH-major] Adenomatous Polyposis Coli Protein / metabolism. Calcium / metabolism

[MeSH-minor] Animals. Cell Membrane / metabolism. Cells, Cultured. Glycogen Synthase Kinase 3 / metabolism. Protein-Tyrosine Kinases / metabolism. Transfection. Xenopus

Hazardous Substances Data Bank. CALCIUM, ELEMENTAL .

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 19638276.001).

[ISSN] 1090-2104

[Journal-full-title] Biochemical and biophysical research communications

[ISO-abbreviation] Biochem. Biophys. Res. Commun.

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] United States

[Chemical-registry-number] 0 / Adenomatous Polyposis Coli Protein; EC 2.7.10.1 / Protein-Tyrosine Kinases; EC 2.7.11.1 / glycogen synthase kinase 3 beta; EC 2.7.11.26 / Glycogen Synthase Kinase 3; SY7Q814VUP / Calcium

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Regulation of the adenomatous polyposis coli gene by the miR-135 family in colorectal cancer.

Inactivation of the adenomatous polyposis coli (APC) gene is a major initiating event in colorectal tumorigenesis.

Most of the mutations in APC generate premature stop codons leading to truncated proteins that have lost beta-catenin binding sites.

APC-free beta-catenin stimulates the Wnt signaling pathway, leading to active transcription of target genes.

In the current study, we describe a novel mechanism for APC regulation.

We show that miR-135a&b target the 3' untranslated region of APC, suppress its expression, and induce downstream Wnt pathway activity.

Interestingly, we find a considerable up-regulation of miR-135a&b in colorectal adenomas and carcinomas, which significantly correlated with low APC mRNA levels.

This genetic interaction is also preserved in full-blown cancer cell lines expressing miR-135a&b, regardless of the mutational status of APC.

Thus, our results uncover a miRNA-mediated mechanism for the control of APC expression and Wnt pathway activity, and suggest its contribution to colorectal cancer pathogenesis.

[MeSH-major] Adenomatous Polyposis Coli Protein / genetics. Adenomatous Polyposis Coli Protein / physiology. Colorectal Neoplasms / genetics. Colorectal Neoplasms / metabolism. Gene Expression Regulation, Neoplastic. MicroRNAs / genetics

[MeSH-minor] 3' Untranslated Regions. Cell Line. Cell Line, Tumor. DNA Mutational Analysis. Gene Expression Profiling. HeLa Cells. Humans. Models, Biological. Promoter Regions, Genetic. Signal Transduction. Wnt Proteins / metabolism

Genetic Alliance. consumer health - Colorectal Cancer.

Genetic Alliance. consumer health - Familial Adenomatous Polyposis (FAP).

MedlinePlus Health Information. consumer health - Colorectal Cancer.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 18632633.001).

[ISSN] 1538-7445

[Journal-full-title] Cancer research

[ISO-abbreviation] Cancer Res.

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] United States

[Chemical-registry-number] 0 / 3' Untranslated Regions; 0 / Adenomatous Polyposis Coli Protein; 0 / MicroRNAs; 0 / Wnt Proteins

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Molecular analysis of mutations for the adenomatous polyposis coli (APC) gene in Romanian patients with colorectal cancer.

Mutations in adenomatous polyposis coli (APC) gene have not been previously characterized among Romanian patients with colorectal cancer (CRC).

We initiate this study to detect the mutations in APC gene in blood and tumor samples collected from 16 patients (10 men and 6 women) and blood samples from 21 first and second degree relatives of the patients.

In the same time, we have searched for 5 bp deletions at codon 1061 of APC gene by PAGE and SSCP methods.

In one patient, was detected a deletion of exon 13th of APC gene both in DNA extracted from blood and tumor samples.

Multiple deletions (e.g. in exon 6, 12, and in 15L and 15W regions) in DNA extracted from the tumor sample were detected, but not in DNA probe obtained from blood cells.

Till now, no mutation affecting 1061 codon of APC gene was identified in the patients investigated in our study.

[MeSH-major] Adenomatous Polyposis Coli / genetics. Colorectal Neoplasms / genetics. Genes, APC

[MeSH-minor] Adenomatous Polyposis Coli Protein / genetics. Adult. Aged. Female. Frameshift Mutation. Humans. Male. Middle Aged. Point Mutation. Romania / epidemiology

Genetic Alliance. consumer health - Colorectal Cancer.

Genetic Alliance. consumer health - Familial Adenomatous Polyposis (FAP).

[Email] Email this result item

Email the results to the following email address:   [X] Close

[Cites] J Biol Chem. 2006 Jun 30;281(26):17751-7 [16798748.001]

[Cites] Scand J Gastroenterol. 2002 Sep;37(9):1048-53 [12374230.001]

[Cites] Eur J Cancer. 2002 May;38(7):867-71 [11978510.001]

[Cites] Genes Dev. 2000 Aug 1;14 (15):1837-51 [10921899.001]

[Cites] Hum Mol Genet. 2001 Apr;10(7):721-33 [11257105.001]

[Cites] J Med Genet. 2004 Jan;41(1):e11 [14729851.001]

[Cites] Hum Mutat. 2005 Feb;25(2):125-34 [15643602.001]

[Cites] Dev Cell. 2004 Dec;7(6):871-83 [15572129.001]

[Cites] Clin Gastroenterol Hepatol. 2005 Nov;3(11):1115-23 [16271343.001]

[Cites] J Clin Oncol. 2000 May;18(9):1967-79 [10784639.001]

[Cites] BMJ. 2000 Oct 7;321(7265):886-9 [11021873.001]

[Cites] Hum Mutat. 2001 Oct;18(4):355 [11668620.001]

[Cites] Hum Genet. 2005 Dec;118(3-4):539-40 [16521263.001]

[Cites] Carcinogenesis. 2004 Jul;25(7):1219-26 [14976131.001]

[Cites] Gut. 2001 Apr;48(4):515-21 [11247896.001]

[Cites] Cancer Res. 2003 Sep 15;63(18):5731-7 [14522893.001]

[Cites] J Med Genet. 1999 Jan;36(1):14-20 [9950360.001]

[Cites] Nucleic Acids Res. 1996 Jan 1;24(1):121-4 [8594558.001]

[Cites] Cancer Biol Ther. 2002 Nov-Dec;1(6):685-92 [12642695.001]

[Cites] Hum Mutat. 1998;Suppl 1:S56-7 [9452041.001]

[Cites] Nature. 2003 Feb 13;421(6924):753-6 [12610628.001]

[Cites] Hum Mutat. 2002 Jun;19(6):664 [12007223.001]

(PMID = 20108522.001).

[ISSN] 1844-122X

[Journal-full-title] Journal of medicine and life

[ISO-abbreviation] J Med Life

[Language] eng

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] Romania

[Chemical-registry-number] 0 / Adenomatous Polyposis Coli Protein

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Risk of colorectal neoplasia associated with the adenomatous polyposis coli E1317Q variant.

BACKGROUND: Reports of the risk of colorectal neoplasia associated with a variant of the adenomatous polyposis coli (APC E1317Q) gene are conflicting.

MATERIALS AND METHODS: All study subjects were tested for the APC E1317Q variant at enrollment.

The crude and adjusted risks of neoplasia associated with the E1317Q variant were calculated.

E1317Q was more prevalent among cases: 15 of 458 (3.3%) cases were carriers compared with 11 of 1431 (0.8%) controls [odds ratio (OR) 4.4, 95% CI 2.0-9.6].

When stratified by neoplasia type, adenoma risk was significantly elevated in carriers (OR 4.1, 95% CI 1.8-9.4) but colorectal cancer risk was not (OR 2.1, 95% CI 0.8-5.3).

After adjustment, the E1317Q variant remained a significant predictor of colorectal adenoma (OR 4.6, 95% CI 2.0-10.8).

CONCLUSIONS: The APC E1317Q variant is associated with colorectal neoplasia, particularly colorectal adenomas, but further studies are still needed.

Genetic Alliance. consumer health - Familial Adenomatous Polyposis (FAP).

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 19474113.001).

[ISSN] 1569-8041

[Journal-full-title] Annals of oncology : official journal of the European Society for Medical Oncology

[ISO-abbreviation] Ann. Oncol.

[Language] ENG

[Publication-type] Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] England

[Chemical-registry-number] 0 / Adenomatous Polyposis Coli Protein

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] [Methylation quantification of adenomatous polyposis coli (APC) gene promoter in plasma of lung cancer patients].

BACKGROUND AND OBJECTIVE: The protein encoded by adenomatous polyposis coli (APC) gene participates in the signaling transduction pathway.

Substantial studies have revealed that hypermethylation of APC gene promoter is closely related to the pathogenesis and development of cancer.

This study was to develop a real-time quantitative methylation specific PCR (real-time QMSP) method, and detect the methylation of APC gene promoter in plasma of lung cancer patients.

METHODS: Genomic DNA with methylated APC gene promoter was extracted from the lung cancer cell line NCI-H460 using phenol-chloroform and quantified by spectrophotometric measurements.

The concentration of cell-free methylated APC gene promoter in the plasma samples was quantified by the external reference method with the standard curve constructed using simulated plasma.

Of 78 lung cancer patients, positive methylation of the APC gene promoter was detected in tumor tissues of 40 cases.

Among the 40 lung cancer patients, positive methylation of the APC gene promoter was found in the plasma of 19 patients (47.5%).

The concentrations of methylated APC promoter in the 19 lung cancer patients ranged from 1.67x10(2) to 6.78x10(3) copies/mL, with a median concentration of 1.67x10(3) copies/mL.

No positive methylation of the APC gene promoter was detected in the plasma of 38 lung cancer patients without APC gene methylation in tissues, 31 benign lung diseases and 23 healthy controls.

CONCLUSIONS: The newly developed real-time QMSP method allows the quantitative measurement of APC gene promoter methylation in plasma.

Hypermethylation of the APC gene promoter in plasma is a potential diagnostic marker for lung cancer diagnosis.

[MeSH-major] Adenomatous Polyposis Coli Protein / genetics. DNA Methylation. Genes, APC. Lung Neoplasms / genetics. Promoter Regions, Genetic

Genetic Alliance. consumer health - Familial Adenomatous Polyposis (FAP).

Genetic Alliance. consumer health - Lung Cancer.

[Email] Email this result item

Email the results to the following email address:   [X] Close

(PMID = 19622298.001).

[Journal-full-title] Ai zheng = Aizheng = Chinese journal of cancer

[ISO-abbreviation] Ai Zheng

[Language] chi

[Publication-type] English Abstract; Journal Article; Research Support, Non-U.S. Gov't

[Publication-country] China

[Chemical-registry-number] 0 / Adenomatous Polyposis Coli Protein; 0 / DNA, Neoplasm

   

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Missense polymorphisms in the adenomatous polyposis coli gene and colorectal cancer risk.

PURPOSE: Whereas truncating germline mutations of the adenomatous polyposis coli (APC) gene give rise to familial adenomatous polyposis, missense polymorphisms of APC may confer a weaker risk for colorectal cancer.

METHODS: We sequenced the entire open reading frame of the APC gene and tested for two common MYH mutations in a population-based series of patients with colorectal cancer and 5 to 99 adenomas.

Missense adenomatous polyposis coli alterations identified in this colorectal cancer multiple-polyp population were analyzed in a population-based series of patients with colorectal cancer and healthy control subjects.

RESULTS: Germline APC or mutY human homologue (MYH) alterations were identified in 16 of 39 colorectal cancer-multiple polyp patients.

Four missense APC gene alterations (S130G, E1317Q, D1822V, G2502S) were observed in 13 individuals and 3 additional patients carried presumed pathogenic (APC Y94X, biallelic MYH Y165C and heterozygous MYH G382D) mutations.

When independently assessed in 971 patients with colorectal cancer and 954 healthy control subjects, none of the identified missense APC alterations conferred a significantly increased risk for colorectal cancer, odds ratio (95 percent confidence intervals): S130G = 3.1 (0.29-32.25), E1317Q = 1.08 (0.59-2.74), G2502S = 1 (0.65-1.63), D1822V (heterozygous) = 0.79 (0.64-0.98), D1822V (homozygous) = 0.82 (0.63-1.27).

CONCLUSIONS: Germline missense APC alterations observed in 33 percent of patients with multiple colorectal neoplasms seemed to play a limited role in colorectal cancer risk when independently assessed by a population-based, case-control analysis.

Genetic Alliance. consumer health - Colorectal Cancer.

Genetic Alliance. consumer health - Familial Adenomatous Polyposis (FAP).

MedlinePlus Health Information. consumer health - Colorectal Cancer.

[Email] Email this result item

Email the results to the following email address:   [X] Close

[Cites] Cancer Lett. 2000 Feb 28;149(1-2):203-6 [10737725.001]

[Cites] Hum Mol Genet. 2000 Sep 22;9(15):2215-21 [11001924.001]

[Cites] Genes Chromosomes Cancer. 2001 Feb;30(2):181-6 [11135435.001]

[Cites] Chronic Dis Can. 2000;21(2):81-6 [11007659.001]

[Cites] Cancer Res. 2001 Feb 1;61(3):1000-4 [11221825.001]

[Cites] Eur J Cancer. 2001 Mar;37(4):499-502 [11267860.001]

[Cites] Gastroenterology. 2001 Aug;121(2):282-301 [11487538.001]

[Cites] Br J Cancer. 2001 Aug 17;85(4):523-6 [11506490.001]

[Cites] Cancer Res. 2001 Oct 15;61(20):7616-22 [11606402.001]

[Cites] Ann Epidemiol. 2002 Jan;12(1):27-33 [11750237.001]

[Cites] Nat Genet. 2002 Jan;30(1):25-6 [11743581.001]

[Cites] Am J Epidemiol. 2002 Aug 15;156(4):300-10 [12181099.001]

[Cites] Genet Test. 2002 Winter;6(4):313-7 [12537656.001]

[Cites] Lancet. 2003 Jul 5;362(9377):39-41 [12853198.001]

[Cites] Cancer Epidemiol Biomarkers Prev. 2003 Oct;12(10):1023-8 [14578138.001]

[Cites] Cancer Epidemiol Biomarkers Prev. 2004 Jan;13(1):146-9 [14744747.001]

[Cites] Int J Cancer. 2004 Jul 1;110(4):550-7 [15122587.001]

[Cites] Nat Rev Cancer. 2004 Oct;4(10):769-80 [15510158.001]

[Cites] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968.001]

[Cites] FEBS Lett. 1978 Mar 1;87(1):107-10 [631324.001]

[Cites] N Engl J Med. 1988 Sep 1;319(9):533-7 [2841598.001]

[Cites] Science. 1991 Aug 9;253(5020):661-5 [1651562.001]

[Cites] Cancer Res. 1992 Jul 15;52(14):4055-7 [1319838.001]

[Cites] Ann Hum Genet. 1992 May;56(Pt 2):99-103 [1503398.001]

[Cites] Nature. 1992 Sep 17;359(6392):235-7 [1528264.001]

[Cites] Cell. 1993 Dec 3;75(5):951-7 [8252630.001]

[Cites] J Med Genet. 1995 Jul;32(7):568-71 [7562975.001]

[Cites] Nucleic Acids Res. 1996 Jan 1;24(1):121-4 [8594558.001]

[Cites] Genes Chromosomes Cancer. 1996 Feb;15(2):122-8 [8834176.001]

[Cites] Cell. 1996 Oct 18;87(2):159-70 [8861899.001]

[Cites] J Med Genet. 1996 Oct;33(10):814-9 [8933332.001]

[Cites] Nucleic Acids Res. 1998 Jan 1;26(1):269-70 [9399850.001]

[Cites] Genes Chromosomes Cancer. 1998 Aug;22(4):257-67 [9669663.001]

[Cites] Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10722-7 [9724771.001]

[Cites] J Med Genet. 1999 Jan;36(1):14-20 [9950360.001]

[Cites] Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2322-6 [10051640.001]

[Cites] Hum Mol Genet. 1999 May;8(5):889-97 [10196379.001]

[Cites] J Natl Cancer Inst. 2004 Nov 3;96(21):1631-4 [15523092.001]

[Cites] Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):15992-7 [15520370.001]

(PMID = 18612690.001).

[ISSN] 1530-0358

[Journal-full-title] Diseases of the colon and rectum

[ISO-abbreviation] Dis. Colon Rectum

[Language] ENG

[Grant] United States / NCI NIH HHS / CA / U01 CA074783-06; United States / NCI NIH HHS / CA / CA074783-06; United States / NCI NIH HHS / CA / CA074783-07; United States / NCI NIH HHS / CA / U01 CA074783; United States / NCI NIH HHS / CA / U01 CA074783-07

[Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

[Publication-country] United States

[Other-IDs] NLM/ NIHMS139709; NLM/ PMC2768068