Apoptosis of bovine ovarian surface epithelial cells by Fas antigen/Fas ligand signaling.
Ovarian surface epithelial cells (OSEs), a single layer of cells that cover the surface of the ovary, undergo turnover at the site of follicular rupture at ovulation. Greater than 90% of ovarian cancers arise from the OSEs. The objective of this study was to determine whether OSEs have the capacity to regulate their own demise through expression of Fas antigen (Fas) and Fas ligand (FasL) and activation of Fas-mediated apoptosis. In initial experiments, primary cultures of bovine OSEs responded to treatment with recombinant FasL by undergoing apoptosis. The percentage of cell death was not affected by the presence or absence of serum in the media or by co-treatment with interferon-gamma, a treatment shown to potentiate Fas-mediated apoptosis in a number of cell types. Subsequent experiments tested the ability of stress-inducing drugs, anisomycin and daunorubicin, to promote apoptosis by stimulating an endogenous Fas-FasL pathway in OSEs. Treatment with FasL, anisomycin or daunorubicin induced cell death and this was suppressed by co-treatment with a peptide inhibitor of caspases, ZVAD. Treatment with anisomycin or daunorubicin in the presence of ZVAD increased expression of FasL mRNA and protein but did not alter expression of Fas mRNA or protein. Treatment of OSEs with a recombinant protein that blocks interaction of FasL with Fas (Fas:Fc) reduced apoptosis in response to anisomycin and daunorubicin, indicating that drug-induced apoptosis was mediated at least partially through endogenous Fas-FasL interactions. In summary, OSEs undergo apoptosis in response to stress-inducing drugs through activation of an endogenous Fas pathway.
Margalit
Kate A
KA
Department of Animal Science, Cornell University, Ithaca, New York 14853, USA.
Cowan
Robert G
RG
Harman
Rebecca M
RM
Quirk
Susan M
SM
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D017209:Apoptosis; D061945:Caspase Inhibitors; D002417:Cattle; D002470:Cell Survival; D002478:Cells, Cultured; D003630:Daunorubicin / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D053222:Fas Ligand Protein; D005260:Female; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D010053:Ovary / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D013194:Staining and Labeling; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D048069:Tumor Necrosis Factors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D019014:fas Receptor; D000841:Anisomycin; D003630:Daunorubicin