Estrogenic effects on growth and vitamin D3 receptor levels in human breast cancer cells

RESUMO

Estrogen is essential for growth and development of 30 per cent of malignant breast tumors and concentration of estrogen receptor (ER) is an indicator of hormone dependence. The effects of estradiol-l7beta (E2) on growth promotion and vitamin D (VDR) and progesterone (PR) receptor modulation were evaluated in hormone-dependent (MCF-7, T47D) and -independent (MDA-MB-231) breast carcinoma cells lines. 10(-7)M E2 stimulated the proliferation of MCF-7 and T47D cells the extent of which was correlated to ER content, being sensitive to growth inhibition of 10(-6) M tamoxifen. No effect on growth and PR levels was observed in E2 treated MDA-MB-231 cells. A statistically significant 10(-7)M E(2-)mediated induction of VDR was verified in T47D cells which was abolished by 10(-6)M tamoxifen, revealing an ER-mediated mechanism. 10(-6)M tamoxifen treatment alone upregulated VDR levels in T47D cells, suggesting that this drug may utilize a distinct pathway (ER-independent) for stimulation of VDR content, by a mechanism, now in progress, to be elucidated. These results, taken together, suggest the importance of VDR level assessment as new a prognostic indicator in breast carcinoma.