Type I gonadotropin-releasing hormone receptor mediates the antiproliferative effects of GnRH-II on prostate cancer cells.

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.

• Authors: Marina Montagnani Marelli, Roberta M Moretti, Stefania Mai, Joanna Januszkiewicz-Caulier, Marcella Motta, Patrizia Limonta
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 94 Issue 5 Pg. 1761-7 (May 2009) ISSN: 1945-7197 [Electronic] United States
• PMID: 19190109 (Publication Type: Journal Article)

Chemical References

• GNRHR protein, human
• GNRHR2 protein, human
• RNA, Small Interfering
• Receptors, LHRH
• Cyclic AMP

Topics

• Blotting, Western
• Cell Line, Tumor
• Cell Proliferation
• Cyclic AMP (physiology)
• Fluorescent Antibody Technique
• Gene Silencing
• Humans
• Male
• Prostatic Neoplasms (pathology)
• RNA, Small Interfering (pharmacology)
• Receptors, LHRH (genetics, physiology)
• Reverse Transcriptase Polymerase Chain Reaction
• Transfection