| Project/Area Number |
13672398
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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 |
応用薬理学・医療系薬学
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| Research Institution | Kyoritsu College of Pharmacy |
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Principal Investigator |
SONODA Yoshiko Kyoritsu College of Pharmacy, Department of Biochemistry, Associate Professor, 薬学部, 助教授 (30050743)
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| Co-Investigator(Kenkyū-buntansha) |
KASAHARA Tadashi Kyoritsu College of Pharmacy, Department of Biochemistry, Professor, 薬学部, 教授 (60049096)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | FAK / PI3-kinase / Akt / survival / glioma / apoptosis / cyclin D3 / PKC / Y397F変異体 / アデノウイルス / カスパーゼ-6 / PTEN / Bcl-2 / 還元酵素 |
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| Research Abstract |
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that plays a pivotal role in a signal transduction at integrin-linked cellular adhesions. We have shown that FAK plays a role in the survival for oxidative stress induced apoptosis and the mutated FAK (Y397F-FAK, 397FAK) loses anti-apoptotic function. As the mutated FAK, 397FAK, might function as a dominant negative FAK, we therefore evaluated the mutated FAK as proapoptotic. We introduced 397FAK gene to human glioma cells, T98G using an adenoviral vector (Adv). 397FAK induced FAK degradation and apoptosis in T98G cells. These results suggest that the strategy of blockage of FAK function may be used for anticancer therapeutics.
FAK-overexpressed (HL-60/FAK) cells proliferate much faster than vector-transfected control (HL-60/Vect) cells with a 1.5-fold faster doubling time. Since protein kinase C (PKC) inhibitor or PI3-kinase inhibitor suppressed cell proliferation effectively, both PKC and PI3-kinase pathways are presumed to be involved in the cell proliferation. Among cyclins and CDKs, cyclin D3 expression was particularly prominent in the HL-60/FAK cells. Among PKC family, PKCa, b and h were activated. We assumed that FAK activates PKC and PI3-kinase-Akt pathway, which resulted in marked induction of cyclin D3 expression and CDK activity. We first indicated that FAK-PKC proliferative pathway was activated in FAK overexpressed cells and this pathway is a potential target of the human glioma.
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