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 p rotein, Bcl-2 in MCF-7 human breast cancer cells. Since estrogen-dependent breast tumours can regress following estrogen withdrawal, we hypothesized t hat stable Bcl-2 expression would prevent estrogen-withdrawal induced regre ssion of MCF-7 tumours, We therefore established tumours in ovariectomized female nude mice implanted with an estrogen-release pellet using untransfec ted MCF-7 cells or MCF-7 cells stably transfected with a Bcl-2 cDNA sense o r 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 r egressed means of 49% and 52%, respectively, after estrogen pellet removal whereas Bcl-2 sense rumours were significantly stabilized, Regressing rumou rs displayed characteristics of apoptotic cells, These results show that Bc l-2 can prevent hormone-dependent breast tumour regression and are consiste nt with the notion that decreased Bcl-2 levels following estrogen withdrawa l renders hormone-dependent breast tumour cells sensitive to apoptotic regr ession. (C) 1998 Federation of European Biochemical Societies.