| RRC ID |
77161
|
| 著者 |
Yu J, Leung WK, Lee TL, Tse PC, To KF, Sung JJ.
|
| タイトル |
Promoter hypermethylation of cyclooxygenase-2 in gastric carcinoma.
|
| ジャーナル |
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.
|
| 巻・号 |
22(5)
|
| ページ |
1025-31
|
| 公開日 |
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
|
| リソース情報 |
| ヒト・動物細胞 |
MKN28(RCB1000)
MKN45(RCB1001) |
