2004 Fiscal Year Final Research Report Summary
Analysis of the mechanism of invasive growth of human glioblastomas
| Project/Area Number |
15390429
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Gunma university |
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Principal Investigator |
ISHIUCHI Shogo Gunma university, School of Medicine, assistant Professor, 医学部, 講師 (10312878)
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| Co-Investigator(Kenkyū-buntansha) |
OZAWA Seiji Gunma university, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40049044)
SAITO Nobuhito Gunma university, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (60262002)
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| Project Period (FY) |
2003 – 2004
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| Keywords | glioblastoma / invasive growth / signal transduction / glutamate / AMPA antagonists |
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| Research Abstract |
Recent studies show that Ca^<2+>-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors play an important role in the growth of glioblastomas. However, the signaling pathway controlling the proliferation of glioblastoma cells is poorly understood. Protein kinase B/Akt has a critical role in tumorigenesis and can enhance proliferation and inhibit apoptosis in cancer cells. Here we show that Ca^<2+>-signaling mediated by AMPA receptors regulates the motility and growth of glioma cells through the activation of Akt. Ca^<2+> supplied through the Ca^<2+>-permeable AMPA receptors phosphorylated Akt at Ser 473, thereby facilitating proliferation as well as mobility. A dominant negative form of Akt inhibits the proliferation and migration accelerated by overexpression of Ca^<2+>-permeable AMPA receptors. In contrast, introduction of a constitutively active form of Akt rescued tumor cells from apoptosis induced by their conversion to Ca^<2+>-impermeable receptors by adenovirus-mediated transfer of the GluR2 cDNA. Thus Akt functions as a downstream effector in Ca^<2+>-signaling by AMPA receptors and this pathway may be a novel target in the treatment of glioblastomas.
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