Effect of oestradiol and insulin on the proliferative pattern and on oestrogen and progesterone receptor contents in MCF-7 cells.

In a long-term experiment MCF-7 cells showed an exponential proliferation rate in fetal calf serum while they become quiescent in growth-factor- and steroid-free serum. The mitogenic activity of this cell line was increased by oestradiol and insulin, exposure to both hormones showing a synergic effect. These mitogen-mediated effects are inhibited by genistein a phytoestrogen which, by itself at the doses used, did not affect either the basal proliferation rate or the total protein content. Immunoblotting and Scatchard analysis reveal respectively that insulin increases the oestrogen receptor (ER) content and its binding capacity. The presence of genistein decreases the ER content and completely abolishes the binding capacity of this protein. Insulin is able to increase progesterone receptor (PR) levels while, in the presence of genistein, the above-reported effect was completely abolished. On the basis of the latter data the authors suggest that insulin is able to affect the phosphorylation status of ER and PR, inducing functional changes in both proteins, although this was in the absence of their natural ligands. Indeed, the presence in the medium of a tyrosine kinase inhibitor such as genistein could substantially decrease both ER and PR levels in these cells.