GROWTH-FACTORS IN STEROID-RESPONSIVE PROSTATIC TUMOR-CELLS

Androgens stimulate the growth of prostatic carcinoma, possibly by mod ulating the activity of locally expressed growth factors. Recently, we have shown that an LHRH (or LHRH-like) system exerting an inhibitory action on cell proliferation is present in the human androgen-dependen t prostatic tumor cell line LNCaP. The following experiments have been performed in LNCaP cells to clarify whether LHRH might inhibit cell p roliferation by interfering with the two major mitogenic factors for t hese cells: (a) testosterone (T), the major exogenous stimulating fact or, and (b) epidermal growth factor (EGF), one of the locally produced growth factors. (a) It has been shown that an LHRH agonist (LHRH-A, Z oladex) counteracts the proliferative action of T in a dose-dependent way. To clarify, whether LHRH might interfere with the activity of T i n prostate tumors, LNCaP cells were treated with LHRH agonist over dif ferent time intervals, and the effects of treatment evaluated in terms of expression of androgen receptor mRNA. The data obtained indicate t hat LHRH-A does not affect androgen receptor expression at any time in terval examined (b) LHRH-A inhibits the mitogenic action of ECF on LNC aP cells and significantly reduces the concentration of EGF receptors in these cells. Experiments have been performed to explore whether LHR H-A might alter intracellular signaling mechanisms mediating the activ ity of EGF. In LNCaP cells LHRH-A blocks EGF-induced expression of the c-fos proto-oncogene but does not modify EGF-induced tyrosine phospho rylation of the EGF receptor. These data suggest that, in androgen-dep endent prostate tumors, LHRH might inhibit cell proliferation by inter fering with some but not all of the mechanisms mediating the mitogenic action of EGF. Possible interactions between LHRH and T-activated eve nts still remain to be elucidated.