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Promoter hypomethylation of a novel cancer/testis antigen gene CAGE is correlated with its aberrant expression and is seen in premalignant stage of gastric carcinoma

Cited 99 time in Web of Science Cited 111 time in Scopus
Authors
Cho, Bomsoo; Lee, Hansoo; Jeong, ShinWu; Bang, Yung-Jue; Lee, Hyun Joo; Hwang, Kyu Sang; Kim, Hae-Yeong; Lee, Yun-Sil; Kang, Gyeong Hoon; Jeoung, Doo-Il
Issue Date
2003-07
Citation
Biochemical and Biophysical Research Communications, Vol.307 No.1, pp.52-63
Keywords
CAGEhypomethylationtranscriptionmethylation-specific PCR
Abstract
Previously, we reported the identification and characterization of a novel cancer/testis antigen gene, CAGE, that was expressed in various histological types of tumors, but not in normal tissues, with the exception of the testis. To date, molecular mechanisms for the expression of CAGE have never been studied. In our expression analysis, we found that some cancer cell lines did not express CAGE. The expression of CAGE could be restored in these cell lines by treatment with 5'-aza-2'-deoxycytidine, suggesting that the expression of CAGE is mainly suppressed by hypermethylation. Bisulfite sequencing analysis of the 16 CpG sites of the CAGE promoter in various cancer cell lines and tissues revealed a close relationship between the methylation status of the CAGE promoter and the expression of CAGE. The transient transfection experiments displayed that the methylation of CpG sites inhibited the CAGE promoter activity in luciferase reporter assays. The methylation of the CpG sites inhibited the binding of transcription factors, shown by a mobility shift assay. A methylation-specific PCR analysis revealed that hypomethylation of the CAGE promoter was present at frequencies of more than 60% in breast, gastric, and lung cancers, and hepatocellular carcinomas, and at frequencies of less than 40% in prostate, uterine cervical, and laryngeal cancers. Promoter hypomethylation was found in chronic gastritis (19/55, 34.5%) and liver cirrhosis (13/22, 59%), but not in normal prostate, normal colon, or chronic hepatitis. These results suggest that the methylation status of the CpG sites of CAGE determines its expression, that the hypomethylation of CAGE precedes the development of gastric cancer and hepatocellular carcinoma, and that the high frequencies of hypomethylation of CAGE, in various cancers would be valuable as a cancer diagnostic marker. (C) 2003 Elsevier Science (USA). All rights reserved.
ISSN
0006-291X
URI
http://hdl.handle.net/10371/172976
DOI
https://doi.org/10.1016/S0006-291X(03)01121-5
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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