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首页> 外文期刊>Cellular Oncology: Analytical Cellular Pathology >Independent Induction of Caspase-8 and cFLIP Expression during Colorectal Carcinogenesis in Sporadic and HNPCC Adenomas and Carcinomas
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Independent Induction of Caspase-8 and cFLIP Expression during Colorectal Carcinogenesis in Sporadic and HNPCC Adenomas and Carcinomas

机译：Caspase-8和cFLIP表达的独立诱导在散发性和HNPCC腺瘤和癌的大肠癌发生过程中。

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Background: TNF-Related Apoptosis Inducing Ligand (TRAIL) is a promising agent for the induction of apoptosis in neoplastic tissues. Important determinants of TRAIL sensitivity are two intracellular proteins of the TRAIL pathway, caspase-8 and its anti-apoptotic competitor cellular Flice-Like Inhibitory Protein (cFLIP).Methods: The aim of this study was to investigate basic expression of caspase-8 and cFLIP in normal colorectal epithelium (n= 20), colorectal adenomas (n= 66) and colorectal carcinomas (n= 44) using immunohistochemistry performed on both sporadic and Hereditary Non-Polyposis Colorectal Cancer (HNPCC or Lynch syndrome)-associated adenomas and carcinomas.Results: Expression of both caspase-8 and cFLIP was similar in cases with sporadic and hereditary origin. Expression of caspase-8 in colorectal adenomas and carcinomas was increased when compared to normal colon tissue (P= 0.02). Nuclear, paranuclear as well as cytoplasmic localizations of caspase-8 were detected. Immunohistochemistry revealed an upregulation of cFLIP in colorectal carcinomas in comparison to normal epithelium and colorectal adenomas (P< 0.001). A large variation in the caspase-8/cFLIP ratio was observed between the individual adenomas and carcinomas.Conclusion: Caspase-8 and cFLIP are upregulated during colorectal carcinogenesis. Upregulation of caspase-8 and/or downregulation of cFLIP may be interesting approaches to maximize TRAIL sensitivity in colorectal neoplasms.
机译：背景：TNF相关的凋亡诱导配体（TRAIL）是一种有前途的诱导肿瘤组织凋亡的药物。 TRAIL敏感性的重要决定因素是TRAIL途径的两种细胞内蛋白caspase-8及其抗凋亡竞争性细胞Flice-Like抑制蛋白（cFLIP）。方法：本研究的目的是研究caspase-8和caspase-8的基本表达。使用针对散发性和遗传性非息肉病大肠癌（HNPCC或林奇综合征）相关的腺瘤和癌的免疫组织化学方法，对正常结直肠上皮（n = 20），结直肠腺瘤（n = 66）和结直肠癌（n = 44）中的cFLIP进行分析结果：在散发性和遗传性病例中，caspase-8和cFLIP的表达相似。与正常结肠组织相比，caspase-8在大肠腺瘤和癌中的表达增加（P = 0.02）。 caspase-8的核，副核以及细胞质定位。免疫组织化学显示与正常上皮和大肠腺瘤相比，大肠癌中cFLIP上调（P <0.001）。结论：结直肠癌的发生过程中，Caspase-8和cFLIP的表达上调。 caspase-8的上调和/或cFLIP的下调可能是使结直肠肿瘤中TRAIL敏感性最大化的有趣方法。

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