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.