Abstract
Recent data suggest that the β-catenin/Tcf-4 signaling pathway plays an important role in human cancer tumorigenesis. However, the mechanism of β-catenin/Tcf-4 signaling in tumorigenesis is poorly understood. In this study, we show that Tcf-4 protein levels were significantly elevated in high-grade gliomas in comparison with low-grade gliomas and that Tcf-4 levels correlated with levels of AKT2. Reduction of β-catenin/Tcf-4 activity inhibited glioma cell proliferation and invasion in vitro and tumor growth in vivo. This effect of β-catenin/Tcf-4 activity was mediated by AKT2, and in vivo binding of β-catenin/Tcf-4 to the AKT2 promoter was validated using the chromatin immunoprecipitation assay and luciferase reporter assays. Taken together, we have demonstrated that Tcf-4 is associated with glioma progression and that AKT2 is a new member of the genes that are regulated by β-catenin/Tcf-4.
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 / genetics
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
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Blotting, Western
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Cell Adhesion
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Cell Cycle
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Cell Movement
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Cell Proliferation
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Chromatin Immunoprecipitation
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Disease Progression
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Gene Expression Regulation, Neoplastic*
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Glioma / genetics
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Glioma / metabolism*
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Glioma / pathology*
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Humans
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Immunoenzyme Techniques
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Luciferases / metabolism
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Promoter Regions, Genetic
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Proto-Oncogene Proteins c-akt / genetics*
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Proto-Oncogene Proteins c-akt / metabolism
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Signal Transduction
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Survival Rate
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Tissue Array Analysis
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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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Transcription, Genetic
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Tumor Cells, Cultured
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beta Catenin / genetics
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beta Catenin / metabolism*
Substances
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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TCF4 protein, human
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Transcription Factor 4
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Transcription Factors
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beta Catenin
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Luciferases
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AKT2 protein, human
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Proto-Oncogene Proteins c-akt