IFN-y Induces Cell Growth Inhibition by Fas-mediated Apoptosis: Requirement of STATI Protein for Up-Regulation of Fas and FasL Expression1

The mechanism by which II Vy inhibits tumor cell growth has not been fully understood. Here we report that IFN-y up-regulated the ex pression of Fas and Fas ligand (FasL) on HT29 cells, a human colon adenocarcinoma cell line, and subsequently induced apoptosis of these cells. The kinetics of cell death in IFN-y-treated HT29 cells paralleled the increase in the levels of Fas and FasL expression. We further show that IFN-y up-regulated the expression of Fas and FasL in STATl-transfected U3A cells but not in STATI-deficient U3A cells. Correspondingly, IFN-y induced cell death in STATl-transfected U3A cells but not in STATIdeficient U3A cells. IFN-y-induced cell death was inhibited by caspase-1 inhibitors. Our results suggest that cell growth inhibition by IFN-y is due to apoptosis mediated by Fas and FasL interaction.