| Project/Area Number |
22591050
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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 | Tokyo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
YOKOYAMA Tomohisa 東京医科大学, 医学部, 講師 (40408240)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | オートファジー / チロシンキナーゼ / メシル酸イマチニブ / 小胞体ストレス / 白血病 / 慢性骨髄性白血病 / 細胞保護効果 / プロテアソーム / ユビキチン / アポトーシス |
|---|
| Research Abstract |
Treatment with imatinib mesylate (IM), which is used for targeting therapy for chronic myelogenous leukemia, exhibited an effect of an increased viable cell number of non-BCR-ABL-expressing cell lines by inhibiting spontaneous apoptosis along with autophagy induction. IM attenuated the cytotoxic effects of cytosine arabinoside,tunicamycin, and bortezomib as well as inhibiting cell death with serum-deprived culturein an autophagy-dependent manner. In contrast to autophagy-dependent cytoprotection in response to IM, combined treatment with autophagy inhibitor such as clarithromycin, and proteasome inhibitor, bortezomib potently enhanced endoplasmic reticulum (ER)-stress mediated apoptosis in breast cancer cells and myeloma cells. These lines of evidence suggest that manipulation of autophagy can induce cytoprotective effect via attenuationof ER-stress loading in various kinds of cells including hematopoietic progenitor cells.
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