Induction of cyclooxygenase-2 in Ras-transformed human mammary epithelial cells undergoing apoptosis.
COX-2 expression has been reported to be elevated in several forms of human cancer. The presence of oncogenic ras has been associated with constitutive induction of COX-2, which confers resistance to apoptosis. Contrary to the above notion, we have found that H-ras-transformed human breast epithelial (MCF10A-ras) cells treated with the anticancer drug ET-18-O-CH(3) exhibit an increased expression of COX-2, while they still undergo apoptosis. To determine whether the induction of COX-2 by ET-18-O-CH(3) could contribute to apoptosis in MCF10A-ras cells, the selective COX-2 inhibitor celecoxib (SC-58635) was used. Celecoxib treatment attenuated ET-18-O-CH(3)-induced cell death. Taken together, the above findings suggest that COX-2 up-regulation does not necessarily confer the resistance to apoptosis in ras-transformed cells, but rather may sensitize these cells to apoptotic death.
Na
Hye-Kyung
HK
Laboratory of Biochemistry and Molecular Toxicology, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
Surh
Young-Joon
YJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000502:physiology*; D001940:Breast; D002461:Cell Line, Transformed; D051546:Cyclooxygenase 2; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology* / Q000502:physiology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D011905:Genes, ras; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology; D007527:Isoenzymes / Q000235:genetics*; D008565:Membrane Proteins; D010742:Phospholipid Ethers / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D051381:Rats
D000970:Antineoplastic Agents; D007527:Isoenzymes; D008565:Membrane Proteins; D010742:Phospholipid Ethers; C026659:edelfosine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases