Differential signaling of the GnRH receptor in pituitary gonadotrope cell lines and prostate cancer cell lines

Ludmila Sviridonov, Masha Dobkin-Bekman, Boris Shterntal, Fiorenza Przedecki, Linor Formishell, Shani Kravchook, Liat Rahamim-Ben Navi, Tali Hana Bar-Lev, Marcelo G. Kazanietz, Zhong Yao, Rony Seger, Zvi Naor

Research output: Contribution to journalArticlepeer-review

Abstract

The GnRH receptor (GnRHR) mediates the pituitary functions of GnRH, as well as its anti-proliferative effects in sex hormone-dependent cancer cells. Here we compare the signaling of GnRHR in pituitary gonadotrope cell lines vs. prostate cancer cell lines. We first noticed that the expression level of PKCα, PKCβII and PKCε is much higher in αT3-1 and LβT2 gonadotrope cell lines vs. LNCaP and DU-145 cell lines, while the opposite is seen for PKCδ. Activation of PKCα, PKCβII and PKCε by GnRH is relatively transient in αT3-1 and LβT2 gonadotrope cell lines and more prolonged in LNCaP and DU-145 cell lines. On the otherhand, the activation and re-distribution of the above PKCs by PMA was similar for both gonadotrope cell lines and prostate cancer cell lines. Activation of ERK1/2 by GnRH and PMA was robust in the gonadotrope cell lines, with a smaller effect observed in the prostate cancer cell lines. The Ca2+ ionophore A23187 stimulated ERK1/2 in gonadotrope cell lines but not in prostate cancer cell lines. GnRH, PMA and A23187 stimulated JNK activity in gonadotrope cell lines, with a more sustained effect in prostate cancer cell lines. Sustained activation of p38 was observed for PMA and A23187 in Du-145 cells, while p38 activation by GnRH, PMA and A23187 in LβT2 cells was transient. Thus, differential expression and re-distribution of PKCs by GnRH and the transient vs. the more sustained nature of the activation of the PKC-MAPK cascade by GnRH in gonadotrope cell lines vs. prostate cancer cell lines respectively, may provide the mechanistic basis for the cell context-dependent differential biological responses observed in GnRH interaction with pituitary gonadotropes vs. prostate cancer cells.

Original languageEnglish
Pages (from-to)107-118
Number of pages12
JournalMolecular and Cellular Endocrinology
Volume369
Issue number1-2
DOIs
StatePublished - 30 Apr 2013

Keywords

  • GnRH
  • GnRH receptor
  • MAP kinase
  • Pituitary cells
  • Prostate cancer cells
  • Protein kinase C

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