Estrogen regulation of transforming growth factor-α in ovarian cancer

Transforming growth factor alpha (TGF α ) may be induced by estrogen in estrogen responsive systems and can contribute to the growth-modulatory effects of this hormone. To test whether TGF α contributes to estrogen-regulated growth in ovarian cancers, we have compared the effects of 17 β -estradiol (E 2 ) and TGF α in a range of ovarian carcinoma cell lines. Addition of E 2 to the estrogen receptor (ER)-positive cell lines (PE01, PE04 and PE01 CDDP ) produced a 2–4 fold increase in TGF α protein concentrations in media conditioned by the cells. Both E 2 and TGF α stimulated the growth of the PE01 and PE04 lines and inhibited the growth of the PE01 CDDP line. Furthermore, the E 2 -mediated growth effects could be reversed by an epidermal growth factor (EGF) receptor-targeted antibody. E 2 also down-regulated EGF receptor expression in ER-positive cell lines. In a series of primary ovarian tumors, higher concentrations of ER were associated with an increased percentage of tumors expressing TGF α mRNA and a decreased percentage expressing EGF receptor protein. All these data are consistent with E 2 increasing production of TGF α in ER-positive ovarian cancer and this in turn acting through the EGF receptor to modulate growth in an autocrine manner.