IFN-GAMMA INDUCES CELL-GROWTH INHIBITION BY FAS-MEDIATED APOPTOSIS - REQUIREMENT OF STAT1 PROTEIN FOR UP-REGULATION OF FAS AND FASL EXPRESSION

The mechanism by which IFN-gamma inhibits tumor cell growth has not be en fully understood. Here we report that IFN-gamma up-regulated the ex pression of Fas and Fas ligand (FasL) on HT29 cells, a human colon ade nocarcinoma cell line, and subsequently induced apoptosis of these cel ls. The kinetics of cell death in IFN-gamma-treated HT29 cells paralle led the increase in the levels of Fas and Fast expression. We further show that IFN-gamma up-regulated the expression of Fas and Fast in STA T1-transfected U3A cells but not in STAT1-deficient U3A cells. Corresp ondingly, IFN-gamma induced cell death in STAT1-transfected U3A cells hut not in STAT1-deficient U3A cells. IFN-gamma-induced cell death was inhibited by caspase-1 inhibitors. Our results suggest that cell grow th inhibition by IFN-gamma is due to apoptosis mediated by Fas and Fas t interaction.