APOPTOSIS INDUCED IN HUMAN COLORECTAL-CARCINOMA BY ANTI-FAS ANTIBODY

Background: Apoptosis or programmed cell death has been shown to play an important role in the progression from polyps to carcinomas. Fas/AP O-1 is a cell surface protein that can induce apoptosis in a variety o f cell types upon specific antibody binding. In this study seven human colorectal carcinoma (HCRC) cell lines of varying differentiation wer e analyzed for cell surface Fas expression, Fas-mediated apoptosis, an d correlation of apoptosis with bcl-2 expression. Methods and Results: Using flow cytometry, all seven lines expressed varying amounts of ce ll surface Fas antigen. Exposure to anti-Fas antibody induced cell dea th in all the cell lines, albeit to varying degrees. The rate of apopt osis was quantitated using how cytometry with propidium iodide stainin g of nuclear DNA. The poorly differentiated cell lines had a significa ntly decreased (p < 0.05) anti-Fas sensitivity as compared with the we ll-differentiated lines. Measurement of bcl-2 expression by flow cytom etry showed an inverse correlation with anti-Fas sensitivity. Conclusi ons: This study confirms that HCRC cell lines express Fas antigen and, more importantly, provides the first evidence that exposure to anti-F as antibody can induce apoptosis. Fas-mediated apoptosis in HCRC cell lines may be regulated by bcl-2 and may correlate with the degree of d ifferentiation.