title: GSK-3β regulates tumor growth and angiogenesis in human glioma cells.
abstract: BACKGROUND
  Glioma accounts for the majority of primary malignant brain tumors in adults.
  
  
  METHODS
  Glioma specimens and normal brain tissues were analyzed for the expression levels of GSK-3β and p-GSK-3β (Ser9) by tissue microarray analysis (TMA) and Western blotting. Glioma cells over-expressing GSK-3β were used to analyze biological functions both in vitro and in vivo.
  
  
  RESULTS
  The levels of p-GSK-3β (Ser9), but not total GSK-3β, are significantly up-regulated in glioma tissues compared to normal tissues, and are significantly correlated with the glioma grades. Ectopic expression of GSK-3β decreased the phosphorylation levels of mTOR and p70S6K1; and inhibited β-catenin, HIF-1α and VEGF expression. Forced expression of GSK-3β in glioma cells significantly inhibited both tumor growth and angiogenesis in vivo.
  
  
  CONCLUSIONS
  These results reveal that GSK-3β regulates mTOR/p70S6K1 signaling pathway and inhibits glioma progression in vivo; its inactivation via p-GSK-3β (Ser9) is associated with glioma development, which is new mechanism that may be helpful in developing GSK-3β-based treatment of glioma in the future.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.affiliation: State Key Lab of Reproductive Medicine, Department of Pathology and Collaborative Innovation Center for Cancer Personalized Medicine, Cancer Center, Nanjing Medical University, Nanjing 210029, China.|Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing, University Medical School, Nanjing 210008, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Zhumei
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Department of Environmental Toxicology, University of California-Davis, Davis, CA 94564, USA.
authors.forename: Charlie
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Lab of Reproductive Medicine, Department of Pathology and Collaborative Innovation Center for Cancer Personalized Medicine, Cancer Center, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Lab of Reproductive Medicine, Department of Pathology and Collaborative Innovation Center for Cancer Personalized Medicine, Cancer Center, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Lab of Reproductive Medicine, Department of Pathology and Collaborative Innovation Center for Cancer Personalized Medicine, Cancer Center, Nanjing Medical University, Nanjing 210029, China.|Ninggao Personalized Medicine and Technology Innovation Center, Nanjing 21130, China.
authors.forename: Chengfei
authors.initials: C
authors.lastname: Jiang
authors.affiliation: State Key Lab of Reproductive Medicine, Department of Pathology and Collaborative Innovation Center for Cancer Personalized Medicine, Cancer Center, Nanjing Medical University, Nanjing 210029, China.|Ninggao Personalized Medicine and Technology Innovation Center, Nanjing 21130, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Qian
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yongping
authors.initials: Y
authors.lastname: You
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Ling-Zhi
authors.initials: LZ
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, China.
authors.forename: Lianshu
authors.initials: L
authors.lastname: Ding
authors.affiliation: State Key Lab of Reproductive Medicine, Department of Pathology and Collaborative Innovation Center for Cancer Personalized Medicine, Cancer Center, Nanjing Medical University, Nanjing 210029, China.|Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Bing-Hua
authors.initials: BH
authors.lastname: Jiang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000098:blood supply / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000098:blood supply / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic; D010766:Phosphorylation; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D046888:Tissue Array Analysis; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051176:beta Catenin; C546842:MTOR protein, human; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D038362:Glycogen Synthase Kinase 3
keywords: GSK-3β; angiogenesis; glioma; mTOR; tumor growth