Abstract
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-γ, a synergistic effect on Fas-mediated apoptosis was obtained when CH-11 and interferon-γ were combined.
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Tillman, D., Harwood, F., Gibson, A. et al. Expression of genes that regulate Fas signalling and Fas-mediated apoptosis in colon carcinoma cells. Cell Death Differ 5, 450–457 (1998). https://doi.org/10.1038/sj.cdd.4400369
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DOI: https://doi.org/10.1038/sj.cdd.4400369
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