Fas-mediated apoptosis in seven human prostate cancer cell lines: correlation with tumor stage.
BACKGROUND
Apoptosis, or programmed cell death, can be mediated through an endogenous signaling pathway that emanates from a cell surface receptor known as Fas. Although best recognized for its role in the immune system, recent studies have also suggested a role for Fas in mediating apoptosis in the murine prostate. Little is known, however, regarding the role of Fas-signaling in the human prostate, and if this signaling pathway is abrogated in the development of prostate cancer (PC).


METHODS
In the current study, seven human PC cell lines were evaluated for their sensitivities to Fas-mediated apoptosis, using both morphologic and flow cytometric methods. Fas expression by each cell line was quantitated by immunofluorescence, and gene expression of three putative inhibitory molecules was analyzed.


RESULTS
The differential sensitivities of the cell lines to Fas-mediated apoptosis were found to correlate with the clinical stage of the parental tumors. Specifically, the three most sensitive cell lines were all derived from primary tumors, while the four most resistant cell lines were derived from distant metastases. Immunofluorescent analyses of the PC cell lines revealed that the observed resistance to apoptosis was not due to reduced expression of membrane-bound Fas. Likewise, this resistance did not correlate with increased gene expression of the inhibitory molecules FAP-1, ICE epsilon, and Ich-1S.


CONCLUSIONS
Our results using established PC cell lines support previous studies with prostatic tissue specimens, and suggest that the normal, differentiated prostatic epithelium, as well as locally invasive PCs, have the potential to undergo Fas-mediated apoptosis. Conversely, these studies suggest that metastatic PCs have a reduced apoptotic potential that is mediated by a novel mechanism.
Hedlund
T E
TE
Department of Pathology, University of Colorado Health Sciences Center, Denver 80262, USA.
Duke
R C
RC
Schleicher
M S
MS
Miller
G J
GJ
D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology*; D017209:Apoptosis; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007075:Immunoglobulin M / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000276:immunology / Q000473:pathology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000032:analysis / Q000276:immunology / Q000502:physiology*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D019014:fas Receptor