| Project/Area Number |
14570988
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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 |
Hematology
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| Research Institution | University of the Ryukyus |
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Principal Investigator |
MORI Naoki University of the Ryukyus, Division of Molecular Virology and Oncology, Professor, 大学院・医学研究科, 教授 (10220013)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | HTLV-I / ATL / Akt / PI3 kinase / mTOR / Tax / Apoptosis / Cell cycle / 成人T細胞白血病 / NF-κB |
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| Research Abstract |
Phosphatidylinositol-3 kinase(PI-3K) and its downstream target Akt are activated by many stimuli and are linked to several different signaling pathways. One major activity of Akt is to mediate cell survival in a broad spectrum of cells. In the leukemogenesis of the human T-cell leukemia virus type I(HTLV-I), Tax has been demonstrated to play a critical role. In the present study we analyzed the role of Akt in HTLV-I-infected T cells. In HTLV-I-infected T-cell lines, the activation of Akt was detected in Tax-expressing cells. Tax increased Akt activity through CREB pathway. We demonstrate that inhibition of PI-3K by a specific inhibitor, LY294002, induced apoptosis and G_1 cell cycle arrest in Tax-expressing HTLV-I-infected T-cell lines in vitro. In contrast, peripheral blood mononuclear cells of healthy donors and Tax-unexpressing HTLV-I-infected T-cell lines were resistant to inhibition of PI-3K. LY294002 did not affect NF-κB and AP-1 activity. Next, we investigated the ability of rapamycin, selectively inhibiting the phosphoprotein mTOR downstream of Akt, to block cell cycle progression. We also showed that rapamycin induced G_1 cell cycle arrest in HTLV-I-infected T-cell lines. These results demonstrate that the activation of Akt signaling pathway, excepting for the NF-κB and AP-1, is required for the cell survival of HTLV-I-infected T cells.
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