RRC ID 77161
Author Yu J, Leung WK, Lee TL, Tse PC, To KF, Sung JJ.
Title Promoter hypermethylation of cyclooxygenase-2 in gastric carcinoma.
Journal Int J Oncol
Abstract Overexpression of cyclooxygenase-2 (COX-2) is associated with loss of apoptosis, enhancement of proliferation and tumorigenesis. The role of promoter methylation in the transcriptional silencing of cox-2 gene in human gastric cancer is less determined. We investigated 5 gastric cancer cell lines and 58 primary gastric carcinomas for the presence of promoter hypermethylation in cox-2 gene. Combined methylation-specific polymerase chain reaction analysis and bisulfite sequencing analysis revealed that the cox-2 promoter was methylated in 2 of the gastric cancer cell lines. Treatment with 5-aza-2'-deoxycytidine, a DNA methyltransferase inhibitor, induced COX-2 expression in the methylated gastric cancer cell line. Among the 58 primary gastric cancers, hypermethylation was detected in 25 (43.1%) cases. However, none of the normal gastric tissues showed methylation in cox-2. Promoter hypermethylation was associated with loss of protein expression as determined by immunostaining (p=0.005). Our results indicate that hypermethylation of the CpG island in the cox-2 gene is a major mechanism that mediates transcriptional silencing in a subset of gastric cancers. Thus, gastric cancers with methylation in cox-2 may not be good candidates for treatment with specific COX-2 inhibitors.
Volume 22(5)
Pages 1025-31
Published 2003-5-1
PMID 12684668
MeSH Adenocarcinoma / enzymology Adenocarcinoma / genetics Adenocarcinoma / pathology Adenocarcinoma / surgery Adult Aged Base Sequence Cyclooxygenase 2 DNA Methylation* DNA Primers Female Gastrectomy Gene Expression Regulation, Neoplastic* Humans Immunohistochemistry Isoenzymes / genetics* Male Membrane Proteins Middle Aged Polymerase Chain Reaction Promoter Regions, Genetic* Prostaglandin-Endoperoxide Synthases / genetics* RNA, Messenger / genetics Reverse Transcriptase Polymerase Chain Reaction Stomach Neoplasms / enzymology Stomach Neoplasms / genetics* Stomach Neoplasms / pathology Stomach Neoplasms / surgery Transcription, Genetic Tumor Cells, Cultured
IF 1.95
Human and Animal Cells MKN28(RCB1000) MKN45(RCB1001)