Adenovirus-mediated expression of Fas ligand induces apoptosis of human prostate cancer cells

Several laboratories have reported on the apoptotic potentials of human pro state cancer (PC) cell lines in response to crosslinking of Fas (CD95/APO-1 ) with agonistic anti-Pas antibodies. We have re-evaluated the apoptotic po tentials of seven human PC cell lines using the natural Fas ligand (FasL) i n place of agonistic antibody. First, PC cell lines were tested in a standa rd cytotoxicity assay with a transfected cell line that stably expresses hu man Fast. Next, we developed an adenoviral expression system employing 293 cells that stably express crmA, a poxvirus inhibitor of apoptosis, to analy ze the effects of Fast when expressed internally by the PC cell lines. Our data suggest that the apoptotic potentials of these cell lines were greatly underestimated in previous studies utilizing agonistic anti-Fas antibodies . Lastly, adenoviral-mediated expression of Fast prevented growth and induc ed regression of two human PC cell lines in immunodeficient mice. These pre liminary in vivo results suggest a potential use for adenovirus encoding Fa st as a gene therapy for PC.