Antagonism between estradiol and progestin on Bcl-2 expression in breast-cancer cells.
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.
Laboratoire d'Oncologie Moleculaire, Universite Paris 7-Denis Diderot, France.
M
M
Kandouz
M
M
Siromachkova
D
D
Jacob
B
B
Chretien Marquet
A
A
Therwath
A
A
Gompel
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting; D011282:Pregnenediones / Q000494:pharmacology; D011372:Progestins / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein; D005466:Fluorocarbons
D004958:Estradiol; D004965:Estrogen Antagonists; D011282:Pregnenediones; D011372:Progestins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013629:Tamoxifen; D051028:bcl-2-Associated X Protein; C494826:BAX protein, human; C086511:RU 58668; D005466:Fluorocarbons; C016601:afimoxifene; C020175:16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione