Roles of cFLIPL in Fas-mediated Apoptosis of Colon Cancer

ABSTRACT

PURPOSE: Substantial numbers of the colon cancer cells have been observed to express Fas/Fas ligands, but are resistant to Fas-mediated apoptosis, suggesting that colon tumors might develop the specific mechanisms to overcome Fas-mediated apoptosis. Recently, cellular FLICE-like inhibitory protein (cFLIP) has been identified as an endogenous inhibitor of Fas- or other receptor-mediated apoptosis and its altered high expression has been suspected to be associated with tumor development or progression. This study investigated the prevalence of cFLIPL alterations in colon carcinomas and possible implications in the progression of colon cancers. METHODS: In order to investigate the function of cFLIPL for the development and progression of the colon cancer, we analyzed the expression of the cFLIPL in 58 colon cancer and 6 colon cancer cell lines. RESULTS: The study results demonstrated that cFLIPL is one of the major determinants for sensitivity to Fas-mediated apoptosis in colon cancer cell lines. In addition, we analyzed cFLIPL expression in 58 cases of adenocarcinoma of the colon and showed that cFLIPL, expression was increased in adenocarcinoma as compared to matched normal mucosa. CONCLUSION: Taken together, our data strongly suggested that abnormal overexpression of cFLIPL is a frequent event in colon carcinomas and might contribute to in vivo tumor transformation.