Antagonism between estradiol and progestin on Bcl-2 expression in breast-cancer cells

Int J Cancer. 1996 Sep 27;68(1):120-5. doi: 10.1002/(SICI)1097-0215(19960927)68:1<120::AID-IJC21>3.0.CO;2-E.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Breast Neoplasms / genetics*
  • Estradiol / analogs & derivatives
  • Estradiol / pharmacology*
  • Estrogen Antagonists / pharmacology
  • Gene Expression / drug effects*
  • Humans
  • Immunoblotting
  • Pregnenediones / pharmacology
  • Progestins / pharmacology*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Tamoxifen / analogs & derivatives
  • Tamoxifen / pharmacology
  • Tumor Cells, Cultured
  • bcl-2-Associated X Protein

Substances

  • BAX protein, human
  • Estrogen Antagonists
  • Pregnenediones
  • Progestins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Tamoxifen
  • RU 58668
  • afimoxifene
  • 16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione
  • Estradiol