title: Promoter methylation analysis of WNT/β-catenin pathway regulators and its association with expression of DNMT1 enzyme in colorectal cancer.
abstract: BACKGROUND
  Aberrant DNA methylation as the most important reason making epigenetic silencing of genes is a main mechanism of gene inactivation in patients with colorectal cancer. In this study, we decided to identify promoter methylation status of ten genes encoding WNT negative regulators, and measure the expression of DNMT1 enzyme in colorectal cancer samples.
  
  
  RESULTS
  Aberrant methylation of APC gene was statistically significant associated with age over 50 (p = 0.017), DDK3 with male (p < 0.0001), SFRP4, WIF1, and WNT5a with increasing tumor stage (p = 0.004, p = 0.029, and p = 0.004), SFRP4 and WIF1 with tumor differentiation (p = 0.009 and p = 0.031) and SFRP2 and SFRP5 with histological type (p = 0.001 and p = 0.025). The increasing number of methylated genes correlated with the expression levels of the DNMT1 mRNA.
  
  
  CONCLUSIONS
  The rate of gene promoter methylation of WNT pathway regulators is high in colorectal cancer cells. Hyper-methylation is associated with increased expression of the DNMT1 enzyme.
authors.forename: Nader Mansour
authors.initials: NM
authors.lastname: Samaei
authors.forename: Yaghoub
authors.initials: Y
authors.lastname: Yazdani
authors.forename: Reza
authors.initials: R
authors.lastname: Alizadeh-Navaei
authors.forename: Hossein
authors.initials: H
authors.lastname: Azadeh
authors.affiliation: Golestan Research Center of Gastroenterology and Hepatology-GRCGH, Golestan University of Medical Sciences, Gorgan, Iran. tourajf@yahoo.com.
authors.forename: Touraj
authors.initials: T
authors.lastname: Farazmandfar
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012737:Sex Factors; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D051176:beta Catenin; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human
references.citation: Histopathology. 2009 Nov;55(5):554-63
references.pmid: 19912361
references.citation: Nat Rev Cancer. 2004 Dec;4(12):988-93
references.pmid: 15573120
references.citation: Biochim Biophys Acta. 2012 Jan;1825(1):18-28
references.pmid: 21982838
references.citation: Cancer Res. 2000 Aug 15;60(16):4366-71
references.pmid: 10969779
references.citation: Cell. 2000 Oct 13;103(2):311-20
references.pmid: 11057903
references.citation: Clin Cancer Res. 2009 Oct 1;15(19):6185-91
references.pmid: 19773381
references.citation: Epigenetics. 2009 Jul 1;4(5):307-312
references.pmid: 28001119
references.citation: Carcinogenesis. 2005 Jan;26(1):37-43
references.pmid: 15375009
references.citation: Nat Protoc. 2008;3(6):1101-8
references.pmid: 18546601
references.citation: Cancer Metastasis Rev. 2004 Jan-Jun;23(1-2):29-39
references.pmid: 15000147
references.citation: Cancer. 1997 Nov 1;80(9):1803-4
references.pmid: 9351551
references.citation: World J Gastroenterol. 2006 Nov 28;12(44):7113-7
references.pmid: 17131472
references.citation: Cancer Biol Ther. 2004 Oct;3(10):960-4
references.pmid: 15326380
references.citation: Cancer Res. 2006 Jan 15;66(2):682-92
references.pmid: 16423997
references.citation: CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96
references.pmid: 18287387
references.citation: Br J Cancer. 2011 Jun 7;104(12):1906-12
references.pmid: 21587258
references.citation: Cancer. 2009 Jan 1;115(1):49-60
references.pmid: 19051296
references.citation: N Engl J Med. 2009 Dec 17;361(25):2449-60
references.pmid: 20018966
references.citation: Adv Genet. 2010;70:27-56
references.pmid: 20920744
references.citation: Gynecol Oncol. 2011 Oct;123(1):116-22
references.pmid: 21726894
references.citation: Int J Cancer. 2006 Nov 15;119(10):2272-8
references.pmid: 16981189
references.citation: Surgery. 2008 Sep;144(3):353-66
references.pmid: 18707034
references.citation: Nat Genet. 2004 Jun;36(6):582-4
references.pmid: 15156141
references.citation: Oncogene. 2006 Jan 5;25(1):139-46
references.pmid: 16247484
references.citation: J Appl Genet. 2006;47(4):365-75
references.pmid: 17132902
references.citation: Cancer Res. 2006 Jan 15;66(2):729-35
references.pmid: 16424002