Analysis of the Wnt/B-catenin/TCF4 pathway using SAGE, genome-wide microarray and promoter analysis: Identification of BRI3 and HSF2 as novel targets

  • Cell Signal. 2010 Oct;22(10):1523-35. doi: 10.1016/j.cellsig.2010.05.021.
Ersen Kavak  1 ,  Ayaz Najafov ,  Nuri Ozturk ,  Tuncay Seker ,  Kader Cavusoglu ,  Tolga Aslan ,  Adil Doganay Duru ,  Tahsin Saygili ,  Gerta Hoxhaj ,  Mahmut Can Hiz ,  Durisehvar Ozer Unal ,  Necla Birgül-Iyison ,  Mehmet Ozturk ,  Ahmet Koman
Affiliations
  • 1. Department of Molecular Biology and Genetics, Bogazici University, Istanbul, Turkey. [email protected]
PMID: 20538055 DOI: 10.1016/j.cellsig.2010.05.021
Abstract

The Wnt signaling pathway is involved in many differentiation events during embryonic development and can lead to tumor formation after aberrant activation of its components. beta-catenin, a cytoplasmic component, plays a major role in the transduction of canonical Wnt signaling. The aim of this study was to identify novel genes that are regulated by active beta-catenin/TCF signaling in hepatocellular carcinoma-derived Huh7 cells with high (transfected) and low beta-catenin/TCF activities. High TCF activity Huh7 cells led to earlier and larger tumor formation when xenografted into nude mice. SAGE (Serial Analysis of Gene Expression), genome-wide microarray and in silico promoter analysis were performed in parallel, to compare gene expression between low and high beta-catenin/TCF activity clones, and also those that had been rescued from the xenograft Tumors. SAGE and genome-wide microarray data were compared and contrasted. BRI3 and HSF2 were identified as novel targets of Wnt/beta-catenin signaling after combined analysis and confirming experiments including qRT-PCR, ChIP, luciferase assay and lithium treatment.