Overexpression of cyclooxygenase-2 protein is less frequent in gastric cancers with microsatellite instability.
Overexpression of cyclooxygenase-2 (COX-2) has been reported in gastric cancers. However, the relationship between expression of COX-2 and clinico-pathological or genotypic features has not been elucidated. To address the issue, expression of COX-2 protein was analyzed in 100 gastric cancers as well as 7 gastric cancer cell lines by using immunoblot analysis. Overexpression of COX-2 in cancer tissues compared with matched non-cancerous tissues was found in 70% of cases and was significantly associated with lymphatic involvement, lymph node metastasis and advanced tumor stage. Interestingly, overexpression of COX-2 was less frequent in gastric cancers with microsatellite instability (MSI) than in those without MSI (8/20 vs. 62/80, p < 0.01). Expression of COX-2 protein was detected in some gastric cancer cell lines without MSI at various levels, but not in those with MSI. Our results suggest that overexpression of COX-2 may play an important role in tumor progression of gastric cancer and also support the notion that gastric cancers with and without MSI represent distinctive pathways of carcinogenesis. We also observed a reduction of MSI phenotype after aspirin or sulindac treatment in a hMLH1-defective gastric cancer cell line SNU-1, which lacks COX-2 expression. Int. J. Cancer (Pred. Oncol.) 84:400-403, 1999.
First Department of Internal Medicine, Sapporo Medical University, Chuo-ku, Sapporo, Japan.
H
H
Yamamoto
F
F
Itoh
H
H
Fukushima
Y
Y
Hinoda
K
K
Imai
D048868:Adaptor Proteins, Signal Transducing; D001241:Aspirin / Q000494:pharmacology; D020137:Base Pair Mismatch; D002352:Carrier Proteins; D051546:Cyclooxygenase 2; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics*; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins; D018895:Microsatellite Repeats / Q000235:genetics*; D000070957:MutL Protein Homolog 1; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics; D009367:Neoplasm Staging; D009687:Nuclear Proteins; D010641:Phenotype; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000235:genetics*; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D013467:Sulindac / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D007527:Isoenzymes; C501486:MLH1 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D013467:Sulindac; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000070957:MutL Protein Homolog 1; D001241:Aspirin