Evidence for common signalling pathways of GnRH receptor and Fas in tumors

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T Fuseya1, A Imai, S Horibe

  • 1GIFU UNIV,SCH MED,DEPT OBSTET & GYNECOL,GIFU 500,JAPAN.

Oncology Reports
|May 20, 2011
PubMed

Insights

This study investigated if Fas and GnRH receptors share signaling pathways. Results suggest a partial overlap in signal transduction, impacting phosphatidylinositol kinase activity in tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Fas receptor mediates apoptosis in various cell types.
  • Gonadotropin-releasing hormone (GnRH) analogs induce apoptosis in GnRH receptor-bearing tumors.

Purpose of the Study:

  • To investigate potential shared signal transduction pathways between Fas and GnRH receptors.
  • To analyze Fas-linked responses in plasma membranes of GnRH receptor-bearing tumors.

Main Methods:

  • Screening of surgically removed gynecological tumors for Fas and GnRH receptor expression.
  • Isolation of plasma membranes from tumors.
  • Assessing phosphatidylinositol (PtdIns) kinase activity via [gamma-P-32]ATP phosphorylation of PtdIns in response to anti-Fas antibody (N-18) and GnRH analog (buserelin).

Main Results:

  • Plasma membranes showed inhibited PtdIns kinase activity upon exposure to both anti-Fas antibody (N-18) and buserelin.
  • Inhibition of PtdIns phosphorylation by N-18 was dose-dependent, with maximal effect at 300 ng/ml (60% decrease).
  • The inhibitory effects of N-18 and buserelin were not additive, indicating a shared pathway.

Conclusions:

  • Data suggest that GnRH analogs and Fas ligands may utilize at least partially similar signal transduction pathways.
  • This finding has implications for understanding apoptosis mechanisms in GnRH receptor-bearing tumors.

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