Recent data suggest that the beta-catenin/Tcf-4 signaling pathway plays an important role in human cancer tumorigenesis. However, the mechanism of beta-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 beta-catenin/Tcf-4 activity inhibited glioma cell proliferation and invasion in vitro and tumor growth in vivo. This effect of beta-catenin/Tcf-4 activity was mediated by AKT2, and in vivo binding of beta-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 beta-catenin/Tcf-4.
基金：
China National Natural Scientific FundNational Natural Science Foundation of China [30971136, 30872657]; Tianjin Science and Technology Committee [09JCZDJC17600]; Program for New Century Excellent Talents in UniversityProgram for New Century Excellent Talents in University (NCET) [NCET-07-0615]; Jiangsu Province's Medical Major Talent program [RC2007061]; Jiangsu Province's Natural Science FoundationNatural Science Foundation of Jiangsu Province [BK2008475]; Jiangsu Higher Education Institutions
医学