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.
Copyright 2010 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
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Carcinoma, Hepatocellular / genetics
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Carcinoma, Hepatocellular / metabolism
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Carcinoma, Hepatocellular / pathology
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Cell Line, Tumor
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Cell Proliferation
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Gene Expression Profiling
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Gene Expression Regulation, Neoplastic
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Genome
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Glycogen Synthase Kinase 3 / antagonists & inhibitors
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Glycogen Synthase Kinase 3 beta
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Heat-Shock Proteins / genetics*
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Humans
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Lithium Chloride / pharmacology
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Liver Neoplasms / genetics
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Liver Neoplasms / metabolism
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Liver Neoplasms / pathology
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Membrane Proteins / genetics*
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Mice
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Mice, Nude
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Nerve Tissue Proteins / genetics*
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Oligonucleotide Array Sequence Analysis
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Promoter Regions, Genetic*
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Signal Transduction
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Transcription Factor 4
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Transcription Factors / genetics*
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Transcription Factors / metabolism*
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Wnt Proteins / metabolism*
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beta Catenin / metabolism*
Substances
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BRI3 protein, human
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Heat-Shock Proteins
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Membrane Proteins
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Nerve Tissue Proteins
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TCF4 protein, human
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Transcription Factor 4
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Transcription Factors
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Wnt Proteins
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beta Catenin
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HSF2 protein, human
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Glycogen Synthase Kinase 3 beta
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Glycogen Synthase Kinase 3
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Lithium Chloride