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β-连环蛋白/TCF信号通路对人肺癌细胞系中livin的转录调控

Transcriptional regulation of livin by beta-catenin/TCF signaling in human lung cancer cell lines.

作者信息

Yuan Dong, Liu Liqun, Gu Dayong

机构信息

Department of Thoracic Surgery, The Affiliated Hospital of Weifang Medical College, Weifang, Shandong Province 261031, PR China.

出版信息

Mol Cell Biochem. 2007 Dec;306(1-2):171-8. doi: 10.1007/s11010-007-9567-6. Epub 2007 Jul 28.

Abstract

Wnt/beta-catenin signaling emerged as a critical pathway in human lung carcinogenesis by regulating the livin promoter activity. This study clarified that livin was a direct target gene of beta-catenin/TCF signaling pathway in non-small cell lung cancer (NSCLC) cells. First, we observed that livin mRNA was up-regulated by LiCl treatment in culture of A549 and 103H cell lines. In addition we found that the activity of livin promoter is increased considerably by activation of beta-catenin and could be blocked by a dominant negative form of DeltaTCF4. Furthermore, we identified a TCF binding site located at -1476/-1470 of the livin promoter which is crucial to the response of beta-catenin. At last, chromatin immunoprecipitation (ChIP) assay was performed and the result indicated that beta-catenin/TCF complex binds to the putative TCF binding site of the livin promoter in A549 and 103H cell lines. Our results suggest that livin is transcriptionally regulated by beta-catenin/TCF signaling in human NSCLC cell lines.

摘要

Wnt/β-连环蛋白信号通路通过调节生存素启动子活性,成为人类肺癌发生过程中的关键信号通路。本研究阐明,在非小细胞肺癌(NSCLC)细胞中,生存素是β-连环蛋白/TCF信号通路的直接靶基因。首先,我们观察到在A549和103H细胞系培养中,LiCl处理可上调生存素mRNA水平。此外,我们发现激活β-连环蛋白可显著增加生存素启动子的活性,且该活性可被显性负性形式的DeltaTCF4阻断。此外,我们在生存素启动子的-1476/-1470处鉴定出一个TCF结合位点,该位点对β-连环蛋白的反应至关重要。最后,进行了染色质免疫沉淀(ChIP)分析,结果表明在A549和103H细胞系中,β-连环蛋白/TCF复合物与生存素启动子的假定TCF结合位点结合。我们的结果表明,在人类NSCLC细胞系中,生存素受β-连环蛋白/TCF信号通路的转录调控。

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