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GSK-3β regulates tumor growth and angiogenesis in human glioma cells.
- Source :
-
Oncotarget [Oncotarget] 2015 Oct 13; Vol. 6 (31), pp. 31901-15. - Publication Year :
- 2015
-
Abstract
- Background: Glioma accounts for the majority of primary malignant brain tumors in adults.<br />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.<br />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.<br />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.
- Subjects :
- Animals
Blotting, Western
Brain Neoplasms blood supply
Brain Neoplasms genetics
Brain Neoplasms pathology
Cell Line, Tumor
Disease Progression
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Glioma blood supply
Glioma genetics
Glioma pathology
Glycogen Synthase Kinase 3 genetics
Glycogen Synthase Kinase 3 beta
Humans
Hypoxia-Inducible Factor 1, alpha Subunit genetics
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
Male
Mice, Inbred BALB C
Mice, Nude
Phosphorylation
Ribosomal Protein S6 Kinases, 70-kDa metabolism
Signal Transduction
TOR Serine-Threonine Kinases metabolism
Tissue Array Analysis
Transfection
Vascular Endothelial Growth Factor A genetics
Vascular Endothelial Growth Factor A metabolism
beta Catenin genetics
beta Catenin metabolism
Brain Neoplasms enzymology
Cell Proliferation
Glioma enzymology
Glycogen Synthase Kinase 3 metabolism
Neovascularization, Pathologic
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 6
- Issue :
- 31
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 26388612
- Full Text :
- https://doi.org/10.18632/oncotarget.5043