Progestin effects on long-term growth, death, and bcl-xL in breast cancer cells

The effect of progestins on proliferation of breast cancer has been a contr oversial area. We have consistently reported progestin stimulation of proli feration in the progesterone receptor-rich human breast cancer cell line T4 7D. Other authors, under other conditions, have agreed that progestins stim ulate, but for just one turn of the cell cycle. To our knowledge, this is t he first in vitro report to show progestin stimulation of human breast canc er cell growth for multiple, probably unlimited, cell cycles, while control cells are dying. This is accompanied by progestin up-regulation of the ant iapoptotic protein bcl-xL, no effect on the pro-apoptotic protein bar, and, surprisingly, diminution of the antiapoptotic protein bcl-2. Thus, progest ins both serve as survival factors and stimulate proliferation, implying a possible similar role in breast cancer patients. The data support the notio n that many patients may benefit more from combined antiprogestin-antiestro gen therapy than from antiestrogen alone, and suggest bcl-x(L) as a possibl e target for breast cancer therapy. (C) 2000 Academic Press.