Tuesday, August 12, 2008
Transcriptional regulation of livin by β-catenin/TCF signaling in human lung cancer cell lines
Abstract Wnt/β-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 β-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 β-catenin and could be blocked by a dominant negative form of ΔTCF4. Furthermore, we identified a TCF binding site located at −1476/−1470 of the livin promoter which is crucial to the response of β-catenin. At last, chromatin immunoprecipitation (ChIP) assay was performed and the result indicated that β-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 β-catenin/TCF signaling in human NSCLC cell lines.
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