Ryu B K, Lee M G, Chi S G, Kim Y W, Park J H
Department of Pathology, College of Medicine, Kyung Hee University, #1 Hoegi-dong, Dongdaemoon-Goo, Seoul 130-701, Korea.
J Pathol. 2001 May;194(1):15-9. doi: 10.1002/path.835.
During tumour progression, cancer cells use diverse mechanisms to escape from apoptosis-inducing stimuli, which may include receptor internalization, inhibition of signal pathways, and regulation of specific sets of genes. Substantial numbers of colon cancer cells have been observed to express Fas/Fas ligand, but are resistant to Fas-mediated apoptosis, suggesting that colonic tumours might develop 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 a suspected association with tumour development or progression. In an effort to investigate the prevalence of cFLIP(L) alterations in colon carcinomas and their possible implications for the progression of colon cancers, cFLIP(L) expression was analysed in adenocarcinomas and adenomatous polyps of colon, with matched normal tissues, at RNA and protein levels, by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. cFLIP(L) transcripts were constitutively expressed in colon cancers and expression levels were significantly higher in carcinomas than in normal tissues (p<0.05). Overexpression of cFLIP(L) protein was found exclusively in carcinoma cells in all matched sets analysed and approximately three-fold induction was detected in cancer cells (p<0.05). The expression of cFLIP(L) protein was not significantly altered in adenomatous polyps compared with normal tissues. Taken together, these results strongly suggest that abnormal overexpression of cFLIP(L) is a frequent event in colon carcinomas and might contribute to in vivo tumour transformation.
在肿瘤进展过程中，癌细胞利用多种机制逃避凋亡诱导刺激，这些机制可能包括受体内化、信号通路抑制以及特定基因集的调控。大量结肠癌细胞被观察到表达Fas/Fas配体，但对Fas介导的凋亡具有抗性，这表明结肠肿瘤可能发展出特定机制来克服Fas介导的凋亡。最近，细胞FLICE样抑制蛋白（cFLIP）已被鉴定为Fas或其他受体介导的凋亡的内源性抑制剂，其异常高表达与肿瘤发展或进展存在可疑关联。为了研究cFLIP(L)改变在结肠癌中的普遍性及其对结肠癌进展的可能影响，通过半定量逆转录-聚合酶链反应（RT-PCR）和免疫组织化学在RNA和蛋白质水平分析了结肠癌、结肠腺瘤性息肉及其匹配的正常组织中的cFLIP(L)表达。cFLIP(L)转录本在结肠癌中组成性表达，癌组织中的表达水平显著高于正常组织（p<0.05）。在所有分析的匹配组中，仅在癌细胞中发现cFLIP(L)蛋白过表达，并且在癌细胞中检测到约三倍的诱导（p<0.05）。与正常组织相比，腺瘤性息肉中cFLIP(L)蛋白的表达没有显著改变。综上所述，这些结果强烈表明cFLIP(L)的异常过表达在结肠癌中是常见事件，并且可能有助于体内肿瘤转化。
