Yuan Dong, Liu Liqun, Gu Dayong
Department of Thoracic Surgery, The Affiliated Hospital of Weifang Medical College, Weifang, Shandong Province 261031, PR China.
Mol Cell Biochem. 2007 Dec;306(1-2):171-8. doi: 10.1007/s11010-007-9567-6. Epub 2007 Jul 28.
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.
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。