The role of estradiol receptor in the proliferative activity of vanadate on MCF-7 cells.

Vanadate stimulates growth of the estradiol-responsive MCF-7 cells in the absence of estrogens through a mechanism requiring tyrosine kinase activity. The proliferative effect of vanadate is mediated by estradiol receptor, and is inhibited by three antiestrogens, hydroxytamoxifen, ICI 164,384, and ICI 182,780. Estradiol abolishes the inhibitory effect of ICI 164,384 or ICI 182,780. Before stimulating cell proliferation, vanadate induces accumulation of tyrosine phosphorylation in several proteins including estradiol receptor and epidermal growth factor receptor. In addition, vanadate increases the binding activity of the estradiol receptor for its ligand. This is the first evidence of in vivo association between estradiol receptor tyrosine phosphorylation and its hormone-binding activation. Antiestrogens abolish the vanadate effect on estradiol receptor and epidermal growth factor receptor phosphorylation and reduce it on general protein tyrosine phosphorylation. These findings show that vanadate, apparently through estradiol receptor tyrosine phosphorylation, triggers activity of this receptor, which in turn stimulates protein tyrosine phosphorylation and induces cell proliferation.