Estrogen withdrawal-induced human breast cancer tumour regression in nude mice is prevented by Bcl-2

FEBS Lett. 1998 Dec 4;440(3):403-8. doi: 10.1016/s0014-5793(98)01499-9.

Abstract

We recently showed that estrogen induces expression of the anti-apoptotic protein, Bcl-2 in MCF-7 human breast cancer cells. Since estrogen-dependent breast tumours can regress following estrogen withdrawal, we hypothesized that stable Bcl-2 expression would prevent estrogen-withdrawal induced regression of MCF-7 tumours. We therefore established tumours in ovariectomized female nude mice implanted with an estrogen-release pellet using untransfected MCF-7 cells or MCF-7 cells stably transfected with a Bcl-2 cDNA sense or antisense expression vector. All tumours grew at similar rates indicating that Bcl-2 levels have no effect on tumour formation. After removal of the estrogen pellet, Bcl-2 antisense tumours and untransfected MCF-7 tumours regressed means of 49% and 52%, respectively, after estrogen pellet removal whereas Bcl-2 sense tumours were significantly stabilized. Regressing tumours displayed characteristics of apoptotic cells. These results show that Bcl-2 can prevent hormone-dependent breast tumour regression and are consistent with the notion that decreased Bcl-2 levels following estrogen withdrawal renders hormone-dependent breast tumour cells sensitive to apoptotic regression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Estrogens / administration & dosage
  • Estrogens / physiology*
  • Female
  • Humans
  • Mammary Neoplasms, Experimental / etiology
  • Mammary Neoplasms, Experimental / metabolism*
  • Mammary Neoplasms, Experimental / physiopathology
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Proto-Oncogene Proteins c-bcl-2 / pharmacology*
  • Substance Withdrawal Syndrome
  • Tumor Cells, Cultured

Substances

  • Estrogens
  • Proto-Oncogene Proteins c-bcl-2