Adenovirus-mediated expression of Fas ligand induces apoptosis of human prostate cancer cells.
Several laboratories have reported on the apoptotic potentials of human prostate cancer (PC) cell lines in response to crosslinking of Fas (CD95/APO-1) with agonistic anti-Fas antibodies. We have re-evaluated the apoptotic potentials of seven human PC cell lines using the natural Fas ligand (FasL) in place of agonistic antibody. First, PC cell lines were tested in a standard cytotoxicity assay with a transfected cell line that stably expresses human FasL. Next, we developed an adenoviral expression system employing 293 cells that stably express crmA, a poxvirus inhibitor of apoptosis, to analyze the effects of FasL 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 FasL prevented growth and induced regression of two human PC cell lines in immunodeficient mice. These preliminary in vivo results suggest a potential use for adenovirus encoding FasL as a gene therapy for PC.
Hedlund
T E
TE
Department of Immunology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Meech
S J
SJ
Srikanth
S
S
Kraft
A S
AS
Miller
G J
GJ
Schaack
J B
JB
Duke
R C
RC
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002455:Cell Division; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D011212:Poxviridae / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics*; D015843:Serpins / Q000235:genetics / Q000494:pharmacology; D014161:Transduction, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D014764:Viral Proteins
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D015843:Serpins; D014764:Viral Proteins; C074641:interleukin-1beta-converting enzyme inhibitor