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Dr. Sarkis H. Meterissian MD, Maria Kontogiannea BSc, John Po BSc, Gitte Jensen PhD, Brett Ferdinand MD
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Background: Apoptosis or programmed cell death has been shown to play an important role in the progression from polyps to carcinomas. Fas/APO-1 is a cell surface protein that can induce apoptosis in a variety of cell types upon specific antibody binding. In this study seven human colorectal carcinoma (HCRC) cell lines of varying differentiation were analyzed for cell surface Fas expression, Fas-mediated apoptosis, and correlation of apoptosis withbcl-2 expression.
Methods and Results: Using flow cytometry, all seven lines expressed varying amounts of cell surface Fas antigen. Exposure to anti-Fas antibody induced cell death in all the cell lines, albeit to varying degrees. The rate of apoptosis was quantitated using flow cytometry with propidium iodide staining of nuclear DNA. The poorly differentiated cell lines had a significantly decreased (p<0.05) anti-Fas sensitivity as compared with the well-differentiated lines. Measurement ofbcl-2 expression by flow cytometry showed an inverse correlation with anti-Fas sensitivity.
Conclusions: This study confirms that HCRC cell lines express Fas antigen and, more importantly, provides the first evidence that exposure to anti-Fas antibody can induce apoptosis. Fas-mediated apoptosis in HCRC cell lines may be regulated bybcl-2 and may correlate with the degree of differentiation.
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