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  • Title: High level of cFLIP correlates with resistance to death receptor-induced apoptosis in bladder carcinoma cells.
    Author: Jönsson G, Paulie S, Grandien A.
    Journal: Anticancer Res; 2003; 23(2B):1213-8. PubMed ID: 12820373.
    Abstract:
    BACKGROUND: The cellular form of FLICE-inhibitory protein (cFLIP) blocks death receptor-induced apoptosis and has been implicated in tumour progression. cFLIP interacts with caspase-8, thereby preventing activation of the caspase cascade. In this study we investigated the endogenous expression of cFLIP and caspase-8 in bladder carcinoma cells in relation to their sensitivity to death receptor-ligation. MATERIALS AND METHODS: Apoptosis was induced by agonistic anti-CD95 mAbs or recombinant TRAIL and quantified by the TUNEL technique. The relative mRNA expression of cFLIP and caspase-8 was quantified by real-time PCR. Stable expression of cFLIP long (cFLIPL) was obtained by retroviral transduction. RESULTS: The relative ratio of cFLIP and caspase-8 was directly correlated to resistance to anti-CD95 or TRAIL-mediated apoptosis. Overexpression of cFLIPL shifted the responsiveness towards resistant status. CONCLUSION: cFLIP is an important determinant of susceptibility to death receptor-induced apoptosis in bladder carcinomas and could function as a prognostic marker for death receptor sensitivity in future immune therapy.
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