Aberrant promoter CpG islands methylation of tumor suppressor genes in cholangiocarcinoma.
Aberrant DNA methylation of 5'-CpG islands located within gene promoters has been identified as a mechanism for transcriptional inactivation of tumor suppressor genes. To ascertain the mechanism of gene promoter hypermethylation in cholangiocarcinoma (CC), we investigated promoter methylation status of the candidate genes ID4, DLC-1, and SFRP1 in 41 CCs, 19 adjacent nontumor tissues, and 15 normal liver tissues using methylation-specific PCR (MSP). The frequencies of DNA methylation were: 57.5% (23 of 40) for ID4, 14.3% (5 of 35) for DLC-1, and 63.4% (26 of 41) for SFRP1, respectively. In contrast, a low frequency of methylation was detected in nontumor tissues. In addition, hypermethylated status of these genes was detected in three kinds of CC cell lines. Moreover, the downregulated expression of these genes in these cells was restored by treatment with 5-aza-2'-deoxycytidine, a DNA methyltransferase inhibitor. Taken together, these results suggest that aberrant DNA methylation may contribute to the tumorigenesis of cholangiocarcinoma.
Uhm
Kyung-Ok
KO
Institute of Human Genetics, Department of Anatomy, Brain Korea 21 Biomedical Sciences, Korea University College of Medicine, Seoul, 136-705, Korea.
Lee
Eun Soo
ES
Lee
Yun Mi
YM
Kim
Hyeon Soo
HS
Park
Young-Nyun
YN
Park
Sun-Hwa
SH
D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008875:Middle Aged; D011401:Promoter Regions, Genetic