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

Ersen Kavak; 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

doi:10.1016/j.cellsig.2010.05.021

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. Epub 2010 Jun 9.

Authors

Ersen Kavak¹, 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

Affiliation

¹ Department of Molecular Biology and Genetics, Bogazici University, Istanbul, Turkey. ersen.kavak@ki.se

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
Carcinoma, Hepatocellular / genetics
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / pathology
Cell Line, Tumor
Cell Proliferation
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genome
Glycogen Synthase Kinase 3 / antagonists & inhibitors
Glycogen Synthase Kinase 3 beta
Heat-Shock Proteins / genetics*
Humans
Lithium Chloride / pharmacology
Liver Neoplasms / genetics
Liver Neoplasms / metabolism
Liver Neoplasms / pathology
Membrane Proteins / genetics*
Mice
Mice, Nude
Nerve Tissue Proteins / genetics*
Oligonucleotide Array Sequence Analysis
Promoter Regions, Genetic*
Signal Transduction
Transcription Factor 4
Transcription Factors / genetics*
Transcription Factors / metabolism*
Wnt Proteins / metabolism*
beta Catenin / metabolism*

Substances

BRI3 protein, human
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Heat-Shock Proteins
Membrane Proteins
Nerve Tissue Proteins
TCF4 protein, human
Transcription Factor 4
Transcription Factors
Wnt Proteins
beta Catenin
HSF2 protein, human
Glycogen Synthase Kinase 3 beta
Glycogen Synthase Kinase 3
Lithium Chloride

Associated data

GEO/GSE11956