Fas, a cell surface receptor, mediates cell death by means of apoptosis in a variety of cell types. GnRH receptor-bearing tumors undergo apoptosis with GnRH analogs. To examine whether Fas and GnRH receptor share the same signal transduction pathway, we attempted to detect Fas-linked responses within plasma membrane isolated from GnRH receptor-bearing tumors. Surgically removed gynecological tumors were screened for Fas and GnRH receptor expression prior to analyses. The plasma membranes from these tumors responded to anti-Fas antibody (N-18) exposure with an inhibition in phosphatidylinositol (PtdIns) kinase activity, analogous to response to GnRH analog (buserelin) exposure; the activity was measured as phosphorylation from [gamma-P-32]ATP of exogenous substrate PtdIns by the purified plasma membranes. This inhibition was dependent on the N-18 dose, and a maximal effect occurred at 300 ng/ml with 60% decrease in PtdIns phosphorylation. The maximal inhibitory effects of N-18 and buserelin were not additive on PtdIns kinase inhibition; inhibition by both N-18 and GnRH analog was no greater than with either one alone. These data might suggest that there may be at least some similarity in signal transduction pathway utilized by GnRH analogs and Fas ligands.

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