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
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.