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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cells, Cultured
  • Chromatin Immunoprecipitation
  • Gene Expression Regulation*
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics*
  • Inhibitor of Apoptosis Proteins / metabolism
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • TCF Transcription Factors / metabolism*
  • Transcription, Genetic*
  • Transcriptional Activation
  • beta Catenin / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • BIRC7 protein, human
  • Inhibitor of Apoptosis Proteins
  • Neoplasm Proteins
  • RNA, Messenger
  • TCF Transcription Factors
  • beta Catenin