Cyclooxygenase-2 overexpression in MCF-10F human breast epithelial cells inhibits proliferation, apoptosis and differentiation, and causes partial transformation
✍ Scribed by Suying Lu; Guo Yu; Yonghong Zhu; Michael C. Archer
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- French
- Weight
- 283 KB
- Volume
- 116
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
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 ∼ 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. © 2005 Wiley‐Liss, Inc.