EVIDENCE FOR COMMON SIGNALING PATHWAYS OF GNRH RECEPTOR AND FAS IN TUMORS

Fas, a cell surface receptor, mediates cell death by means of apoptosi s in a variety of cell types. GnRH receptor-bearing tumors undergo apo ptosis with GnRH analogs. To examine whether Fas and GnRH receptor sha re the same signal transduction pathway, we attempted to detect Fas-li nked responses within plasma membrane isolated from GnRH receptor-bear ing tumors. Surgically removed gynecological tumors were screened for Fas and GnRH receptor expression prior to analyses. The plasma membran es from these tumors responded to anti-Fas antibody (N-18) exposure wi th an inhibition in phosphatidylinositol (PtdIns) kinase activity, ana logous to response to GnRH analog (buserelin) exposure; the activity w as measured as phosphorylation from [gamma-P-32]ATP of exogenous subst rate PtdIns by the purified plasma membranes. This inhibition was depe ndent on the N-18 dose, and a maximal effect occurred at 300 ng/ml wit h 60% decrease in PtdIns phosphorylation. The maximal inhibitory effec ts 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 eit her one alone. These data might suggest that there may be at least som e similarity in signal transduction pathway utilized by GnRH analogs a nd Fas ligands.