Increased expression of cFLIP(L) in colonic adeno carcinoma

During tumour progression, cancer cells use diverse mechanisms to escape fr om apoptosis-inducing stimuli, which may include receptor internalization, inhibition of signal pathways, and regulation of specific sets of genes. Su bstantial numbers of colon cancer cells have been observed to express Fas/F as ligand, but are resistant to Fas-mediated apoptosis, suggesting that col onic tumours might develop specific mechanisms to overcome Fas-mediated apo ptosis. Recently, cellular FLICE-like inhibitory protein (cFLIP) has: been identified as an endogenous inhibitor of Fas- or other receptor-mediated ap optosis and its altered high expression has a suspected association with tu mour development or progression. In an effort to investigate the prevalence of cFLIP(L) alterations in colon carcinomas and their possible implication s for the progression of colon cancers, cFLIPL expression was analysed in a denocarcinomas and adenomatous polyps of colon, with matched normal tissues , at RNA and protein levels, by semi-quantitative reverse transcription-pol ymerase chain reaction (RT-PCR) and immunohistochemistry. cFLIPL transcript s were constitutively expressed in colon cancers and expression levels sere significantly higher in carcinomas than in normal tissues (p < 0.05), Over expression of cFLIP(1). protein was found exclusively in carcinoma cells in all matched sets analysed and approximately three-fold induction was detec ted in cancer cells (p<0.05). The expression of cFLIP, protein nas not sign ificantly altered in adenomatous polyps compared with normal tissues. Taken together, these results strongly suggest that abnormal overexpression of c FLIP(L); is a frequent event in colon carcinomas and might contribute to in vivo tumour transformation. Copyright (C) 2001 John Wiley & Sons, Ltd.