EFFECT OF ESTRADIOL AND INSULIN ON THE PROLIFERATIVE PATTERN AND ON ESTROGEN AND PROGESTERONE-RECEPTOR CONTENTS IN MCF-7 CELLS

In a long-term experiment MCF-7 cells showed an exponential proliferat ion rate in fetal calf serum while they become quiescent in growth-fac tor- and steroid-free serum. The mitogenic activity of this cell line was increased by oestradiol and insulin, exposure to both hormones sho wing a synergic effect. These mitogen-mediated effects are inhibited b y genistein a phytoestrogen which, by itself at the doses used, did no t affect either the basal proliferation rate or the total protein cont ent. Immunoblotting and Scatchard analysis reveal respectively that in sulin increases the oestrogen receptor (ER) content and its binding ca pacity. The presence of genistein decreases the ER content and complet ely 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 a ffect the phosphorylation status of ER and PR, inducing functional cha nges in both proteins, although this was in the absence of their natur al ligands. Indeed, the presence in the medium of a tyrosine kinase in hibitor such as genistein could substantially decrease both ER and PR levels in these cells.