Sex steroids and growth factors in mammary cancer

We have studied the effect of mitogens on the proliferation of the human breast cancer cell line MCF7 under growth factor-defined culture conditions. Under these conditions MCF7 cells showed the strict hormone dependence that has been established in vivo (in nude mice). E2, insulin or insulin-like growth factors were found to be essential mitogens for these cells. E2 synergistically stimulated proliferation in combination with suboptimal doses of these growth factors. This latter combination of mitogens could be important for in vivo growth regulation of hormone-dependent breast tumours. Synthetic progestins used in oral contraceptives slightly inhibited proliferation induced by estrogen alone. On the other hand, in combination with low concentrations of insulin these progestins synergistically stimulated proliferation, but only at pharmacological concentrations. This effect seems to be due to cross-reactivity of these compounds or their metabolites with the estrogen receptor. The effects of the progestins on the MCF7 cell line indicate that the use of these compounds at high concentrations may be unfavourable, but do not support a role for them in stimulating breast tumour proliferation at the low plasma concentrations that are reached in oral contraceptive users.