MCF-7 HUMAN MAMMARY ADENOCARCINOMA CELL-DEATH IN-VITRO IN RESPONSE TOHORMONE-WITHDRAWAL AND DNA-DAMAGE

Anti-oestrogens exert a tumoristatic effect on estrogen-receptor-posit ive breast carcinomas in vivo. At a cellular level this may reflect in hibition of cell proliferation and/or cell death counterbalanced by co ntinued proliferation of a cell subpopulation, We evaluated the MCF-7 human mammary adenocarcinoma cell line as an in vitro model to study t he effects of the novel oestrogen antagonist ICI 182,720 on cell popul ation dynamics (cell gain vs. cell loss). After oestrogen-withdrawal m onolayer cell number declined over 10 days, accompanied by cell detach ment, This decrease in viable cell number war elevated 2-fold by ICI 1 82,780. Detached cells exhibited DNA fragments of 50 and 300 kbp, typi cal of apoptotic cells, However, internucleosomal cleavage to 180 bp i nteger fragments was not seen, and these detached cells exhibited a mo rphology which was not consistent with apoptosis. The remaining attach ed monolayer cells were morphologically viable (>99%) with regard to b oth nuclear morphology and plasma membrane integrity. There was no dif ference in cell cycle phase distribution between oestrogen-withdrawn a nd ICI 182,780-treated cells; both induced accumulation in GI phase, M CF-7 cells were also exposed to a variety of DNA damaging agents known to induce apoptosis in other cell types, We could demonstrate only li mited induction of morphologically recognisable apoptosis in MCF-7 cel ls treated with methyl methanesulphonate. Our results add to the contr oversy surrounding the ability of the MCF-7 cell line to undergo apopt osis in vitro in response to anti-oestrogen therapies. (C) 1995 Wiley- Liss, Inc.