Abstract

Proliferation of human mammary cancer cells exposed to 27-hydroxycholesterol, a novel SERM Cruz P., Epuñán M.J., Torres C.G., Ramírez M.E., Valladares L.E., Sierralta W.D. Laboratorio de Nutrición y Regulación Metabólica, INTA-Universidad de Chile. Mammary tumors containing estradiol receptor α (ERα) frequently become resistant to treatments with either antiestrogens or inhibitors of the local production of estradiol (E2).Searching for explanations for this phenomenon, we analyzed the effects of 27-hydroxycholesterol (27OHC), a novel selective ER modulator, on the growth of mammary cancer cells in culture. We evaluated the stimulatory effect of this oxysterol on the expansion of ERα+ tumor cell lines in the absence or presence of the pure antagonist ICI 182,780 (ICI). Analyses of BrdU incorporation, demostrated tha 27OHC promotes significant changes in the fraction of MCF7 cells entering the S phase of the cell-cycle. The effects of 27OHC and estradiol were identically neutralized by ICI. Low concentrations of simvastatin abolished the stimulatory activity of 27OHC but not that of E2. The presence of 27OHC did not affect the proliferation of MCF10 nor of ERα- tumor cells in culture. In addition, the oxysterol diminished the adherence of ERα+ cells. We postulate that the effects of 27OHC are relevant in infiltrated tumors, since the activity of local macrophages -known 27OHC producers- will enhance breast cancer growth. We speculate that the increased growth of breast cancer seen in obese patients may be related from increased 27OHC circulatory levels. FONDECYT 1090057.