Induction of cyclooxygenase-2 in Ras-transformed human mammary epithelial cells undergoing apoptosis

Ann N Y Acad Sci. 2002 Nov:973:153-60. doi: 10.1111/j.1749-6632.2002.tb04626.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / physiology*
  • Breast
  • Cell Line, Transformed
  • Cyclooxygenase 2
  • Epithelial Cells / cytology
  • Epithelial Cells / enzymology*
  • Epithelial Cells / physiology
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects
  • Genes, ras*
  • Humans
  • Intestinal Mucosa / enzymology
  • Isoenzymes / genetics*
  • Membrane Proteins
  • Phospholipid Ethers / pharmacology*
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Rats


  • Antineoplastic Agents
  • Isoenzymes
  • Membrane Proteins
  • Phospholipid Ethers
  • edelfosine
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases