Estrogen withdrawal-induced human breast cancer tumour regression in nude mice is prevented by Bcl-2.
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.
Pratt
M A
MA
Department of Pharmacology, University of Ottawa, Ont, Canada. cpratt@uottawa.ca
Krajewski
S
S
Menard
M
M
Krajewska
M
M
Macleod
H
H
Reed
J C
JC
D000818:Animals; D017209:Apoptosis; D004967:Estrogens / Q000008:administration & dosage / Q000502:physiology*; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome; D014407:Tumor Cells, Cultured
D004967:Estrogens; D019253:Proto-Oncogene Proteins c-bcl-2