| Project/Area Number |
15591286
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Nagasaki University |
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Principal Investigator |
MATSUDA Naoki (2006) Nagasaki University, Center for Frontier Life Sciences, Professor, 先導生命科学研究支援センター, 教授 (00304973)
奥村 寛 (2003-2005) 長崎大学, 大学院・医歯薬学総合研究科, 教授 (00073130)
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| Co-Investigator(Kenkyū-buntansha) |
IHARA Makoto Nagasaki University, Graduate School of Biomedical Sciences, Assistant Professor, 大学院医歯薬学総合研究科, 助手 (60175213)
MORITA Naoko Nagasaki University, Graduate School of Biomedical Sciences, Research Technician, 大学院医歯薬学総合研究科, 技術職員 (90380972)
松田 尚樹 先導生命科学研究支援センター, 教授 (00304973)
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| Project Period (FY) |
2003 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2006: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2005: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2004: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | cell mobility / metastasis / X-ray / integrin / laminin / FAK / ERK / p53 / 癌転移 / 細胞外マトリックス / 放射線照射 / 神経膠芽腫細胞 / P53 |
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| Research Abstract |
The aim of this project was to better understand the cellular and molecular mechanisms underlying enhanced tumor invasion by X-ray irradiation, especially focusing on cell mobility and intracellular signaling originated from the interaction of cell adherence molecules with extracellular matirix. The glioma cell line A172 exhibited directed migration to laminin (LM) as revealed by the migration assay which quantitate the number of migrated cells through a micropore membrane filter. Exposure of the cells to 3Gy of X ray, which decreases cell survival to approximately 70% of unirradiated, resulted in enhanced migration associated with elevated expression of integrin-β1 subunit that binds to LM. A172M cells, a p53 mutant cell line at R248W, did not show any changes in mobility and integrin-β1 expression following X-ray irradiation. Tie enhanced interaction of integrin and LM by the irradiation was confirmed by the phosphorylations of focal adhesion kinase (FAK). Furthermore, ERK1/2, a member of MAPK and one of the signaling molecules downstream of FAK, was also phosphorylated after X-ray irradiation. These findings suggests that X-ray irradiation at a sublethal dose induces tumor invasion by, at least in part, promoting the interaction of LM and integrins which leads to elevated cellular signaling. Furthermore, p53 might play some part in that signal pathways.
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