title: High β-catenin/Tcf-4 activity confers glioma progression via direct regulation of AKT2 gene expression.
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.
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052, China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Zhang
authors.forename: Kai
authors.initials: K
authors.lastname: Huang
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Shi
authors.forename: Jian
authors.initials: J
authors.lastname: Zou
authors.forename: Yingyi
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhifan
authors.initials: Z
authors.lastname: Jia
authors.forename: Anling
authors.initials: A
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.forename: Xiao
authors.initials: X
authors.lastname: Yue
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Yongping
authors.initials: Y
authors.lastname: You
authors.forename: Peiyu
authors.initials: P
authors.lastname: Pu
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Kang
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002448:Cell Adhesion; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D015996:Survival Rate; D046888:Tissue Array Analysis; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051176:beta Catenin; D008156:Luciferases; C494921:AKT2 protein, human; D051057:Proto-Oncogene Proteins c-akt