Effect of progestin treatment on estradiol-and growth factor-stimulated breast cancer cell lines

Reports about the effects of progestins on cell proliferation are contradictory. We investigated the effect of progesterone, medroxyprogesterone acetate, megestrol acetate, ORG 2058 and the antiprogestin RU 486 on two hormone-dependent cell lines, T47D and MCF-7 (characterized by a different content of PgR). The aim of the study was to understand the eventual ability of progestins to interfere with cell proliferation stimulated by estradiol and various growth factors (TGF-a, IGF-I, IGF-II).

MCF-7 and T47D cells were maintained in DMEM/F12 medium supplemented with 2% FCS while experiments were carried out in the same culture medium using DCC-stripped FCS.

In the absence of estradiol, all tested progestins generally tended to stimulate cell growth in the T47D cell line, but in the MCF-7 cell line only the highest concentrations (10(-6) M and 10(-7) M) were found to be stimulatory. In contrast, in the presence of 10(-8) M estradiol, progestins tended to inhibit cell growth stimulation in MCF-7 and T47D cell lines. The antiprogestin RU 486 exerted a stimulatory effect similar to that promoted by estradiol itself in MCF-7 cells. Instead, in T47D cells, RU 486 did not modify cell growth in the absence of estradiol, but tended to counteract the estradiol-promoted cell proliferation. In MCF-7 cells, medroxyprogesterone acetate and megestrol acetate were also able to effectively counteract the cell growth induced by TGF-alpha. However, none of these progestins was able to abolish cell proliferation promoted by IGF-I or IGF-II.

We therefore concluded that failure to respond to progestin treatment may be due to the very heterogeneous nature of human breast tumors and to the inability of these molecules to interfere with the IGF-R pathway.