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DLEC1 is a functional 3p22.3 tumour suppressor silenced by promoter CpG methylation in colon and gastric cancers

Authors
 J Ying  ;  FF Poon  ;  J Yu  ;  H Geng  ;  AHY Wong  ;  G-H Qiu  ;  HK Goh  ;  SY Rha  ;  L Tian  ;  ATC Chan  ;  JJY Sung  ;  Q Tao 
Citation
 BRITISH JOURNAL OF CANCER, Vol.100(4) : 663-669, 2009 
Journal Title
 BRITISH JOURNAL OF CANCER 
ISSN
 0007-0920 
Issue Date
2009
MeSH
Cell Line, Tumor ; Chromosomes, Human, Pair 3/genetics ; Chromosomes, Human, Pair 3/metabolism ; Colon/metabolism ; Colonic Neoplasms/genetics* ; Colonic Neoplasms/metabolism ; CpG Islands* ; DNA Methylation* ; Female ; Gene Expression Regulation, Neoplastic* ; Gene Silencing ; Humans ; Male ; Promoter Regions, Genetic* ; Stomach Neoplasms/genetics* ; Stomach Neoplasms/metabolism ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism*
Keywords
tumour suppressor gene (TSG) ; DLEC1 ; CpG island ; methylation ; colon and gastric cancers
Abstract
Promoter CpG methylation of tumour suppressor genes (TSGs) is an epigenetic biomarker for TSG identification and molecular diagnosis. We screened genome wide for novel methylated genes through methylation subtraction of a genetic demethylation model of colon cancer (double knockout of DNMT1 and DNMT3B in HCT116) and identified DLEC1 (Deleted in lung and oesophageal cancer 1), a major 3p22.3 TSG, as one of the methylated targets. We further found that DLEC1 was downregulated or silenced in most colorectal and gastric cell lines due to promoter methylation, whereas broadly expressed in normal tissues including colon and stomach, and unmethylated in expressing cell lines and immortalised normal colon epithelial cells. DLEC1 expression was reactivated through pharmacologic or genetic demethylation, indicating a DNMT1/DNMT3B-mediated methylation silencing. Aberrant methylation was further detected in primary colorectal (10 out of 34, 29%) and gastric tumours (30 out of 89, 34%), but seldom in paired normal colon (0 out of 17) and gastric (1 out of 20, 5%) samples. No correlation between DLEC1 methylation and clinical parameters of gastric cancers was found. Ectopic expression of DLEC1 in silenced HCT116 and MKN45 cells strongly inhibited their clonogenicity. Thus, DLEC1 is a functional tumour suppressor, being frequently silenced by epigenetic mechanism in gastrointestinal tumours
Files in This Item:
T200903270.pdf Download
DOI
10.1038/sj.bjc.6604888
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/104851
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