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Brain Res. 2010 Dec 17;1366:27-37. doi: 10.1016/j.brainres.2010.10.032. Epub 2010 Oct 20.

Interruption of β-catenin suppresses the EGFR pathway by blocking multiple oncogenic targets in human glioma cells.

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  • 1Laboratory of Neuro-Oncology, Tianjin Neurological Institute, PR China.

Abstract

Malignant gliomas are the most common type of intrinsic central nervous system (CNS) tumors with high mortality and morbidity. β-catenin is overexpressed in human glioblastoma and knockdown of β-catenin inhibits glioblastoma cell proliferation and invasive ability, and induces apoptotic cell death. Furthermore, treating the nude mice carrying established subcutaneous LN229 gliomas with siRNA targeting β-catenin intratumorally also delayed the tumor growth. However, the mechanisms of down-regulation of β-catenin that represses glioblastoma malignancy behavior remain to be elucidated. We utilized text-mining of MEDLINE abstracts with natural language processing to establish the β-catenin biologic association network, and identified several interactions of this network with the EGFR pathway. In both in vitro and in vivo studies, our results confirmed down-regulation of β-catenin induced reduced expression of EGFR, STAT3 and AKT1 mRNA and protein, besides, the level of phosphorylated Akt also decreased. A similar reduction in expression of CyclinD1, MMP2 and MMP9, downstream genes of the EGFR pathway, was observed. These results suggest that the Wnt/β-catenin pathway regulates glioma cell proliferation and invasion, in part via the EGFR pathway.

Copyright © 2010 Elsevier B.V. All rights reserved.

[PubMed - indexed for MEDLINE]
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