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Aberrant methylation of the specific CpG island portion regulates cyclooxygenase-2 gene expression in human gastric carcinomas

Cited 22 time in Web of Science Cited 26 time in Scopus
Authors
Hur, Keun; Song, Sang Hyun; Lee, Hye Seung; Kim, Woo Ho; Bang, Yung-Jue; Yang, Han Kwang
Issue Date
2003-10
Citation
Biochemical and Biophysical Research Communications, Vol.310 No.3, pp.844-851
Keywords
methylationCpG islandcyclooxygenase-2gastric carcinoma
Abstract
Although it has been well established that overexpression of cyclooxygenase-2 (Cox-2) favors tumorigenesis and metastasis, the molecular mechanism that regulates Cox-2 expression has not been well defined in gastric carcinoma. Aberrant methylation of the CpG island is known to be one of the powerful mechanisms for the suppression of gene expression, and usually, CpG islands are very rich in promoter region and exon-1 region. But, it is controversial whether Cox-2 gene expression is regulated by methylation of promoter region or exon-1 region. In this study, we examined whether the hyper-methylation mediated transcriptional silencing of Cox-2 also occurred in human gastric carcinoma tissues and which portion of CpG island methylation is important in Cox-2 gene expression. Genomic DNAs from human gastric carcinoma tissues were treated with three methylation-sensitive restriction enzymes and then Southern blot analysis was performed. Out of 30 primary gastric tumor samples, 26 cases (86.6%) showed overexpression of Cox-2. Four cases (13.3%) with relatively decreased Cox-2 gene expression were associated with the presence of aberrant methylation of Cox-2 CpG island. We also found that methylation of promoter region and not exon-1 region is related with the transcriptional silencing of Cox-2 in gastric carcinoma cancer by detailed methylation mapping using bisulfite sequencing analysis. Our results suggest that the DNA methylation-mediated transcriptional silencing of Cox-2 is a predominant mechanism for the down-regulation of Cox-2 expression in human gastric carcinoma. Furthermore, the results suggest that methylation of not exon-1 region but promoter region is important to regulation of Cox-2 gene expression. (C) 2003 Elsevier Inc. All rights reserved.
ISSN
0006-291X
URI
https://hdl.handle.net/10371/172977
DOI
https://doi.org/10.1016/j.bbrc.2003.09.095
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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