Cyclooxygenase-2 overexpression in MCF-10F human breast epithelial cells inhibits proliferation, apoptosis and differentiation, and causes partial transformation

Int J Cancer. 2005 Oct 10;116(6):847-52. doi: 10.1002/ijc.21142.


To investigate the effects of cyclooxygenase-2 (COX-2) overexpression on breast cancer development, we stably transfected MCF-10F human breast epithelial cells with an expression vector containing human COX-2 cDNA oriented in the sense (10F-S) or antisense (10F-AS) direction. As expected, 10F-S cells expressed elevated levels of COX-2 protein, whereas this protein was undetectable in the 10F-AS cells. Prostaglandin E(2) production in these cells reflected COX-2 levels. The 10F-S cells had a significantly decreased rate of proliferation compared to 10F-AS or parental cells, and a delay in progression through the G(1) phase of the cell cycle. COX-2 overexpression also caused resistance to detachment-induced apoptosis (anoikis) as well as an inhibition of differentiation in cells cultured in Matrigel. Furthermore, after approximately 20 passages in culture, 10F-S cells developed fibroblast-like features, expressed vimentin, and formed foci of dense growth when cultured at confluence, suggesting that the cells were undergoing epithelial to mesenchymal transition (EMT). The 10F-S cells, however, were unable to grow in soft agar or form tumors in nude mice, suggesting that they were only partially transformed. Our observations suggest that COX-2 overexpression in human breast epithelial cells will predispose the mammary gland to carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anoikis
  • Apoptosis / physiology*
  • Breast / cytology*
  • Breast / enzymology
  • Cell Adhesion
  • Cell Cycle
  • Cell Differentiation / physiology*
  • Cell Division / physiology*
  • Cell Line
  • Cell Transformation, Neoplastic*
  • Cyclooxygenase 2
  • Dinoprostone / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / enzymology*
  • Female
  • Genetic Vectors
  • Humans
  • Membrane Proteins
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Recombinant Proteins / metabolism
  • Transfection


  • Membrane Proteins
  • Recombinant Proteins
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone