Role of proliferation and apoptosis in net growth rates of human breast cancer cells (MCF-7) treated with oestradiol and/or tamoxifen

Studies on growth regulation in vitro to a large extent rely on comparison of growth curves. However, these do not discriminate between the relative contributions of the mitotic rate and the apoptotic rate to the net growth rate. In the present study, differential effects of 17 beta-oestradiol (E(2), 10(-8) M) and/or tamoxifen (TAM, 10(-6) M) on proliferation and apoptosis have been examined and related to growth curves of a subline of the human breast cancer cell line MCF-7 adapted to grow at low serum concentrations. Counting of cells and scoring of labelling and apoptotic indices were performed at the start of the experiment and 3, 6 and 9 days after changing the experimental media. The results demonstrate that apoptosis in this subline is constitutively expressed, that E(2) protects (at least partly) against apoptosis and stimulates proliferation, resulting in an increased (net) growth rate and final cell pool size, and that TAM has a weak cytostatic effect and stimulates apoptosis strongly, resulting in a decreased (net) growth rate and final cell pool size. When E(2) and TAM are added simultaneously to the medium, the cytotoxic effect of TAM is partly counterbalanced by the protective role of E(2), resulting in a reduced apoptotic rate that, however, is at a higher level than in cultures grown with E(2) only. As the cytostatic role of TAM is partly abolished by E(2), the combined effect of E(2) and TAM results in a final (net) growth rate and cell pool size intermediary to cells grown with E(2) or TAM alone.