Activation of mitogen-activated protein kinases by a splice variant of GHRH receptor

Nektarios Barabutis, Agnieszka Siejka, Andrew V Schally, Norman L Block, Renzhi Cai, Joseph L. Varga

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Hypothalamic GHRH controls the release of GH from the pituitary gland and also acts as a growth factor in a variety of cancers. The mitogenetic activity of GHRH is exerted through the binding to the pituitary type receptor (pGHRH-R) and its splice variants, mainly SV1. The intracellular signaling pathways that are activated upon the binding of GHRH to the SV1 receptor have not been elucidated. HeLa cervical cancer cells do not express GHRH or GHRH receptors (GHRHRs) and thus do not respond to GHRH or GHRH antagonists. In order to elucidate the mechanism of action of SV1 receptor, we transfected HeLacells with plasmids forpcDNA3-GHRHRorpcDNA3-SV1. The transfected cells responded to both GHRH (1-29)NH 2 and GHRH antagonist MZ-5-156, as shown by an increase or decrease respectively in the proliferation rate in vitro and the expression of proliferative cell nuclear antigen. We also demonstrated that when the cells transfected with SV1 plasmid are stimulated withGHRH (1-29)NH 2, SV1 receptor activates the mitogen-activated protein kinases pathway (MAPKs), as shown previously for the cells that express pGHRH-R. Our results show, for the first time, the activation of the MAPKs cascade by the SV1 receptor. Since SV1 receptor is found in various tumors and mediates the responses to GHRH and synthetic antagonists, our findings shed light on the mechanism of action of SV1 receptor in cancer cells.

Original languageEnglish
Pages (from-to)127-134
Number of pages8
JournalJournal of Molecular Endocrinology
Volume44
Issue number2
DOIs
StatePublished - Feb 1 2010

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ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology

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