ru-58668 and 16-alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3-20-dione

Bcl-2 is a key protein involved in the control of apoptosis. Our previous studies on breast and endometrium indicated hormonal regulation of bcl-2 in these tissues. In the present work we have analyzed Bcl-2 and Bax protein expressions in MCF-7 and T47-D, 2 hormone-dependent breast-cancer cell lines, by immunoblots. Estradiol markedly increased Bcl-2 protein content, both in short- and in long-term treatments of MCF-7 cells. Two types of anti-estrogens (4-hydroxytamoxifen and RU 58668) were able to reverse this effect. Also, a synthetic progestin (ORG 2058) was able to decrease the Bcl-2 level in T47-D cells. The level of Bax protein, however, was not affected in the same conditions of hormonal treatments. The level of Bcl-2 expression was 4.5-fold higher in MCF-7 than in MDA-MB 231 (an estradiol-independent cell line). From these results, we infer the existence of hormonal regulation of Bcl-2 expression and evoke a novel role for estradiol and progestin in the genesis of breast cancer.

Topics: bcl-2-Associated X Protein; Blotting, Western; Breast Neoplasms; Estradiol; Estrogen Antagonists; Gene Expression; Humans; Immunoblotting; Pregnenediones; Progestins; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Tamoxifen; Tumor Cells, Cultured