Silencing and CpG island methylation of GSTP1 is rare in ordinary gastric carcinomas but common in Epstein-Barr virus-associated gastric carcinomas.
BACKGROUND
The GSTPI gene encodes for glutathione S-transferase pi (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.


METHODS
The expression of GST-pi and the methylation status of the promoter area of GST-pi were investigated in gastric carcinomas. Eleven human SNUgastric 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%o) 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).


CONCLUSIONS
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.
Kim
Jin
J
Departament of Pathology, Seoul National University College of Medicine, Seoul 110-799, Korea.
Lee
Hye Seung
HS
Bae
Soo In
SI
Lee
You Mie
YM
Kim
Woo Ho
WH
D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D005260:Female; D020868:Gene Silencing; D051549:Glutathione S-Transferase pi / Q000096:biosynthesis / Q000235:genetics*; D004854:Herpesvirus 4, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D014412:Tumor Virus Infections / Q000150:complications / Q000201:enzymology / Q000235:genetics* / Q000821:virology
C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi