Expression of genes that regulate Fas signalling and Fas-mediated apoptosis in colon carcinoma cells.
The expression of genes that regulate Fas-induced apoptosis has been examined in 10 human cultured colon carcinoma cell lines with defined and varied sensitivity to the cytolytic anti-Fas MoAb CH-11. Four lines demonstrated sensitivity to CH-11 (HT29, GC3/c1, TS-, Thy4), and six were resistant to the induction of apoptosis vis Fas. In nine lines expressing Fas, PCR-sequencing indicated that the death domain contained wt sequences. Downstream of Fas, expression of FADD/MORT1 and FLICE, essential components of the DISC, and negative regulators of Fas signalling including sFas, FAP-1 and Bcl-2, showed no correlation between levels of expression and sensitivity to Fas-mediated cytotoxicity. However, levels of the Fas antigen varied by >1000-fold, and correlated with CH-11 sensitivity. Following fourfold elevation in Fas expression in HT29 cells treated with interferon-gamma, a synergistic effect on Fas-mediated apoptosis was obtained when CH-11 and interferon-gamma were combined.
Tillman
D M
DM
Department of Molecular Pharmacology, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee 38105, USA.
Harwood
F G
FG
Gibson
A A
AA
Houghton
J A
JA
D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology; D053200:Fas-Associated Death Domain Protein; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000235:genetics* / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D019014:fas Receptor; D007371:Interferon-gamma; C516742:PTPN13 protein, human; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases