It is now well accepted that locally produced growth factors play a crucial 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 (LNCaP) and androgen-independent (DU 145) prostatic tumor cells, and that LHRH counteracts the mitogenic action of exogenous epidermal growth factor (EGF). The possibility that LHRH might inhibit cell proliferation by interfering with some of the mechanisms mediating the stimulatory action of EGF has been tested. To this purpose, the effects of an LHRH 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 the EGF receptor and completely abrogated the EGF-induced c-fos expression, but did not modify the phosphorylation of the EGF receptor. In DU 145 cells, the LHRH agonist decreased the concentration of EGF-binding sites and substantially counteracted the tyrosine phosphorylation of the EGF receptor, but did not affect the expression of the c-fos proto-oncogene induced by this growth factor. These results suggest that, in prostatic tumor cells, the locally produced LHRH may act as an inhibitory factor which exerts its antiproliferative action by interfering with some of the mechanisms mediating the mitogenic action of EGF. The interaction between the two opposite factors (LHRH and EGF) seems to be different in androgen-dependent and in androgen-independent cells.
LRHR as a growth-inhibitory factor in prostatic tumor cells: possible mechanism of action / P. Limonta, R.M. Moretti, M. Montagnani Marelli, D. Dondi, M. Motta. - In: ENDOCRINE-RELATED CANCER. - ISSN 1351-0088. - 3:3(1996), pp. 211-216.
|Titolo:||LRHR as a growth-inhibitory factor in prostatic tumor cells: possible mechanism of action|
LIMONTA, PATRIZIA (Primo)
MORETTI, ROBERTA MANUELA (Secondo)
DONDI, DONATELLA (Penultimo)
|Settore Scientifico Disciplinare:||Settore BIO/09 - Fisiologia|
Settore BIO/13 - Biologia Applicata
|Data di pubblicazione:||1996|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1677/erc.0.0030211|
|Appare nelle tipologie:||01 - Articolo su periodico|