Abstract
Background: The GSTP1 gene encodes for glutathione S-transferase π (GST-pi), which protects cells from cytotoxic agents. The carcinogenic role of this enzyme is at issue because functional polymorphisms have been shown to be a risk factor of human cancer. Moreover, GST-pi protein loss has frequently been reported in various human cancers. Materials and Methods: The expression of GST-pi and the methylation status of the promoter area of GST-pi were investigated in gastric carcinomas. Eleven human SNU gastric cancer cell lines, PC-3 prostate cancer cell lines, various cancer tissues and normal gastric mucosa tissues were analyzed by immunohistochemistry, in situ hybridization, Western blot and methylation specific PCR. Results: Only 22 (2.0%) out of 1081 cases showed loss of GST-pi expression. Interestingly, 16 out of 22 GST-pi-negative cases were Epstein-Barr virus (EBV)-associated gastric carcinomas. The loss of expression of GST-pi among EBV-associated gastric carcinomas was found to be 27.1% (16/59), but to be 0.6% (6/1022) in EBV-negative gastric carcinomas (p<0.001). Eight out of 16 cases with loss of GST-pi expression showed CpG island methylation in the GSTP1 promoter region, while none of the normal gastric mucosa or EBV-negative gastric carcinomas showed methylation (p<0.001). Conclusion: These findings demonstrate that the loss of GST-pi expression is clustered in a subset of gastric carcinomas with EBV incorporation, and that the methylation of the promoter of the GSTP1 gene is correlated with this loss of GST-pi expression. Our results suggest that GST-pi abrogation by CpG island hypermethylation may account for EBV-associated gastric carcinoma.
Original language | English |
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Pages (from-to) | 4013-4019 |
Number of pages | 7 |
Journal | Anticancer Research |
Volume | 25 |
Issue number | 6 B |
State | Published - Nov 2005 |
Keywords
- DNA methylation
- Glutathione S-transferase pi
- Human herpes virus 4
- Stomach neoplasms