tailieunhanh - Báo cáo khoa học: Gonadotropin-releasing hormone and ovarian cancer: a functional and mechanistic overview

The hypothalamic decapeptide gonadotropin-releasing hormone (GnRH) is well known for its role in the control of pituitary gonadotropin secretion, but the hormone and receptor are also expressed in extrapituitary tissues and tumor cells, including epithelial ovarian cancers. | MINIREVIEW Gonadotropin-releasing hormone and ovarian cancer a functional and mechanistic overview Wai-Kin So Jung-Chien Cheng Song-Ling Poon and Peter C. K. Leung Department of Obstetrics and Gynecology University of British Columbia Vancouver Canada Keywords apoptosis G protein GnRH gonadotropinreleasing hormone growth factor invasion MAPK migration ovarian cancer proliferation Correspondence P. C. K. Leung Department of Obstetrics and Gynecology University of British Columbia 2H30 4490 Oak Street Vancouver BC Canada V6H 3V5 Fax 1 604 875 2717 Tel 1 604 875 2718 E-mail peleung@ Received 7 May 2008 revised 5 August 2008 accepted 15 August 2008 doi The hypothalamic decapeptide gonadotropin-releasing hormone GnRH is well known for its role in the control of pituitary gonadotropin secretion but the hormone and receptor are also expressed in extrapituitary tissues and tumor cells including epithelial ovarian cancers. It is hypothesized that they may function as a local autocrine regulatory system in nonpituitary contexts. Numerous studies have demonstrated a direct antiproliferative effect on ovarian cancer cell lines of GnRH and its synthetic analogs. This effect appears to be attributable to multiple steps in the GnRH signaling cascade such as cell cycle arrest at G0 G1. In contrast to GnRH signaling in pituitary gonadotropes the involvement of Gaq protein kinase C and mitogen-activated protein kinases is less apparent in neoplastic cells. Instead in ovarian cancer cells GnRH receptors appear to couple to the pertussis toxin-sensitive protein Gai leading to the activation of protein phosphatase which in turn interferes with growth factor-induced mitogenic signals. Apoptotic involvement is still controversial although GnRH analogs have been shown to protect cancer cells from doxorubicin-induced apoptosis. Recently data supporting a regulatory role of GnRH analogs in ovarian cancer cell migration invasion have started