Differences between human breast cell lines in susceptibility towards growth inhibition by genistein

Genistein is thought to contribute to the putative breast cancer preventive activity of soya. The mechanisms by which it arrests the growth of breast cells are incompletely understood. In order to explore generic features of the modulation of human breast cell growth by genistein, its effects on cel l lines MCF-7, ZR-75.1, T47-D, MDA-MB 468, MDA-MB 231 and HBL 100 were comp ared. Genistein at 1 muM stimulated growth only in MCF-7 cells. At 10 muM i t arrested the growth of all 6 cell types, however that of T47-D and HBL 10 0 cells only in medium with reduced (2%) fetal calf serum. Genistein induce d apoptosis in only MDA-MB 468 cells. It arrested cells in the G2 stage of the cell cycle in all cell lines except ZR-75.1. Cells differed in their su sceptibility towards inhibition by genistein of phorbol ester-induced proto oncogene c-fos levels, transcription factor activator protein-1 (AP-1) acti vity and extracellular signal-regulated kinase (ERK) activity. Genistein au gmented anisomycin-induced levels of proto-oncogene c-jun in ZR 75.1 and MC F-7 cells. The results suggest that induction of apoptosis, G2 cell cycle a rrest and inhibition of c-fos expression, AP-1 transactivation and ERK phos phorylation may contribute to the growth-inhibitory effect of genistein in some breast cell types, but none of these effects of genistein constitutes a generic mode of growth-arresting action. (C) 2001 Cancer Research Campaig n http://www.bjcancer.com.