LHRH AS A GROWTH-INHIBITORY FACTOR IN PROSTATIC TUMOR-CELLS - POSSIBLE MECHANISM OF ACTION

Citation
P. Limonta et al., LHRH AS A GROWTH-INHIBITORY FACTOR IN PROSTATIC TUMOR-CELLS - POSSIBLE MECHANISM OF ACTION, Endocrine-related cancer, 3(3), 1996, pp. 211-216
Citations number
32
Categorie Soggetti
Endocrynology & Metabolism",Oncology
Journal title
ISSN journal
13510088
Volume
3
Issue
3
Year of publication
1996
Pages
211 - 216
Database
ISI
SICI code
1351-0088(1996)3:3<211:LAAGFI>2.0.ZU;2-0
Abstract
It is now well accepted that locally produced growth factors play a cr ucial role in the regulation of the growth of prostatic carcinoma. In the authors' laboratory it has been shown that an LHRH system, endowed with inhibitory activity, is expressed in both androgen-dependent (LN CaP) and androgen-independent (DU 145) prostatic tumor cells, and that LHRH counteracts the mitogenic action of exogenous epidermal growth f actor (EGF). The possibility that LHRH might inhibit cell proliferatio n by interfering with some of the mechanisms mediating the stimulatory action of EGF has been tested. To this purpose, the effects of an LHR H agonist (Zoladex; LHRH-A) have been studied on the concentration of EGF receptors, and on the EGF-induced tyrosine phosphorylation of the EGF receptor, as well as on the EGF-activated expression of the c-fos proto-oncogene both in LNCaP and in DU 145 cells. The results obtained showed that, in LNCaP cells, LHRH-A decreased the concentrations of t he EGF receptor and completely abrogated the EGF-induced c-fos express ion, but did not modify the phosphorylation of the EGF receptor. In DU 145 cells, the LHRH agonist decreased the concentration of EGF-bindin g sites and substantially counteracted the tyrosine phosphorylation of the EGF receptor, but did not affect the expression of the c-fos prot o-oncogene induced by this growth factor. These results suggest that, in prostatic tumor cells, the locally produced LHRH may act as an inhi bitory factor which exerts its antiproliferative action by interfering with some of the mechanisms mediating the mitogenic action of EGF. Th e interaction between the two opposite factors (LHRH and EGF) seems to be different in androgen-dependent and in androgen-independent cells.