Open AccessHigh -catenin/Tcf-4 activity confers glioma progression via direct regulation of AKT2 gene expression
Author(s) -
Junxia Zhang,
Kai Huang,
Zhendong Shi,
Jian Zou,
Yingyi Wang,
Zhifan Jia,
Anling Zhang,
Lei Han,
Yue Xiao,
Ning Liu,
Tao Jiang,
Yongping You,
Peiyu Pu,
Chunsheng Kang
Publication year - 2011
Publication title -
neuro-oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.005
H-Index - 125
eISSN - 1523-5866
pISSN - 1522-8517
DOI - 10.1093/neuonc/nor034
Subject(s) - carcinogenesis , akt2 , catenin , cancer research , chromatin immunoprecipitation , glioma , tumor progression , beta catenin , cell growth , signal transduction , biology , in vivo , chemistry , microbiology and biotechnology , gene expression , gene , wnt signaling pathway , promoter , akt1 , protein kinase b , genetics
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.