ESTROGEN REGULATION OF TRANSFORMING GROWTH-FACTOR-ALPHA IN OVARIAN-CANCER

Transforming growth factor alpha (TGF alpha) may be induced by estroge n in estrogen responsive systems and can contribute to the growth-modu latory effects of this hormone. To test whether TGF alpha contributes to estrogen-regulated growth in ovarian cancers, we have compared the effects of 17 beta-estradiol (E-2) and TGF alpha in a range of ovarian carcinoma cell lines. Addition of E-2 to the estrogen receptor (ER)-p ositive cell lines (PE01, PE04 and pE01(CDDP)) produced a 2-4 fold inc rease in TGF alpha protein concentrations in media conditioned by the cells. Both E-2 and TGF alpha stimulated the growth of the PE01 and PE 04 lines and inhibited the growth of the pE01(CDDP) line. Furthermore, the E-2-mediated growth effects could be reversed by an epidermal gro wth factor (EGF) receptor-targeted antibody. E-2 also down-regulated E GF receptor expression in ER-positive cell lines. In a series of prima ry ovarian tumors, higher concentrations of ER were associated with an increased percentage of tumors expressing TGF alpha mRNA and a decrea sed percentage expressing EGF receptor protein. All these data are con sistent with E-2 increasing production of TGF alpha in ER-positive ova rian cancer and this in turn acting through the EGF receptor to modula te growth in an autocrine manner. (C) 1998 Elsevier Science Ltd. All r ights reserved.