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

FEBS Letters

Krajewski, Stanislaw²  Pratt, M.A.Christine¹  Reed, John C²  Menard, Michel¹  Macleod, Heather¹  Krajewska, Maryla² 

[1] Department of Pharmacology, University of Ottawa, 451 Smyth Road, Ottawa, Ont. K1H 8M5, Canada;Burnham Institute, Cancer Research Center, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA

关键词: Bcl-2;    Apoptosis;    Breast tumour;    Estrogen;    Regression;    E2;    estrogen;    S.D.;    standard deviation;   

DOI  :  10.1016/S0014-5793(98)01499-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown