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-18-0-CH3 exhibit an increased expression of COX-2, while they still undergo apoptosis. To determine whether the induction of COX-2 by ET-18-0-CH3 could contribute to apoptosis in MCF10A-ras cells, the selective COX-2 inhibitor celecoxib (SC-58635) was used. Celecoxib treatment attenuated ET-18-0-CH3-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.