Background: GnRH-II has been shown to exert a strong antiproliferative action on tumors of the female reproductive system. The data so far reported on the effects of GnRH-II on prostate cancer growth are controversial. Moreover, it is still unclear through which receptor [type I or type II GnRH-receptor (GnRH-R)] GnRH-II might modulate cancer cell proliferation. Objective: The objective of this work was to investigate whether GnRH-II might affect the proliferation of prostate cancer cells and to identify the GnRH-R through which the peptide might exert its activity. Design: We investigated the effects of GnRH-II on prostate cancer cell proliferation. We then transfected PC3 cells with a small interfering RNA targeted to type I GnRH-R. After receptor silencing we evaluated the effects of GnRH-II on cell proliferation and on forskolin-induced intracellular cAMP accumulation. Similar experiments were performed by silencing type II GnRH-R. Results: GnRH-II exerted an antiproliferative activity on prostate cancer cells. Transfection of PC3 cells with a type I GnRH-R small interfering RNA resulted in a significant decrease of the expression of this receptor. After type I GnRH-R silencing: 1) the antiproliferative effect of GnRH-II was completely abrogated; and 2) GnRH-II lost its capacity to counteract the forskolin-induced cAMP accumulation. On the contrary, type II GnRH-R silencing did not counteract the antiproliferative effect of GnRH-II. Conclusions: GnRH-II exerts a specific and significant antiproliferative action on prostate cancer cells. This antitumor effect is mediated by the activation of type I (but not of type II) GnRH-R and by its coupled cAMP intracellular signaling pathway. (J Clin Endocrinol Metab 94: 1761–1767, 2009)

Type I Gonadotropin-Releasing Hormone Receptor Mediates the Antiproliferative Effects of GnRH-II on Prostate Cancer cells / M. Montagnani Marelli, R.M. Moretti, S. Mai, J. Januszkiwicz-Caulier, M. Motta, P. Limonta. - In: THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM. - ISSN 0021-972X. - 94:5(2009 May), pp. 1761-1767. [10.1210/jc.2008-1741]

Type I Gonadotropin-Releasing Hormone Receptor Mediates the Antiproliferative Effects of GnRH-II on Prostate Cancer cells

M. Montagnani Marelli
Primo
;
R.M. Moretti
Secondo
;
S. Mai;M. Motta
Penultimo
;
P. Limonta
Ultimo
2009

Abstract

Background: GnRH-II has been shown to exert a strong antiproliferative action on tumors of the female reproductive system. The data so far reported on the effects of GnRH-II on prostate cancer growth are controversial. Moreover, it is still unclear through which receptor [type I or type II GnRH-receptor (GnRH-R)] GnRH-II might modulate cancer cell proliferation. Objective: The objective of this work was to investigate whether GnRH-II might affect the proliferation of prostate cancer cells and to identify the GnRH-R through which the peptide might exert its activity. Design: We investigated the effects of GnRH-II on prostate cancer cell proliferation. We then transfected PC3 cells with a small interfering RNA targeted to type I GnRH-R. After receptor silencing we evaluated the effects of GnRH-II on cell proliferation and on forskolin-induced intracellular cAMP accumulation. Similar experiments were performed by silencing type II GnRH-R. Results: GnRH-II exerted an antiproliferative activity on prostate cancer cells. Transfection of PC3 cells with a type I GnRH-R small interfering RNA resulted in a significant decrease of the expression of this receptor. After type I GnRH-R silencing: 1) the antiproliferative effect of GnRH-II was completely abrogated; and 2) GnRH-II lost its capacity to counteract the forskolin-induced cAMP accumulation. On the contrary, type II GnRH-R silencing did not counteract the antiproliferative effect of GnRH-II. Conclusions: GnRH-II exerts a specific and significant antiproliferative action on prostate cancer cells. This antitumor effect is mediated by the activation of type I (but not of type II) GnRH-R and by its coupled cAMP intracellular signaling pathway. (J Clin Endocrinol Metab 94: 1761–1767, 2009)
Settore BIO/09 - Fisiologia
Settore BIO/13 - Biologia Applicata
mag-2009
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/68974
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