Development of novel therapeutic strategy against tumor progression using animal model
| Project/Area Number |
21590432
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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 |
Experimental pathology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
KITAGAWA Masanobu 東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (10177834)
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| Co-Investigator(Renkei-kenkyūsha) |
倉田 盛人 東京医科歯科大学, 助教 (40451926)
山本 浩平 東京医科歯科大学, 助教 (50451927)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 疾患モデル動物 / レトロウイルス / DNA損傷 / アポトーシス / p53 / DNA-PK |
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| Research Abstract |
The interaction of viral proteins with host-cellular proteins elicits the activation of cellular signal transduction pathways. Previously, we have clarified that an infection with Friend leukemia virus(FLV) markedly enhanced the IR-induced apoptosis of hematopoietic cells in C3H mice in association with P53, ATM, and DNA-PK. The phenomenon was characterized in vivo by severe anemia when the mice were infected with FLV and then treated with a low dose of total body irradiation(TBI). Viral infection and replication occurred almost cell type-specifically in the hematopoietic cells and thus, the apoptotic enhancement was observed only in the hematopoietic cells. However, p53 knockout mice, Atm knockout mice, and DNA-PK-deficient SCID mice with a C3H background did not exhibit this phenotype. A comparison of apoptotic signals after FLV, TBI, or FLV+TBI treatment of these mice revealed that ATM appeared to be necessary for the general signal transduction of TBI-induced apoptosis, while DNA-PK had a specific role in enhancing p53-dependent apoptosis under FLV infection. The host specificity of this phenomenon was caused by the up-regulated expression of Acinus and minichromosome maintenance(MCM) 2 in C3H mice. We also showed that C3H mouse-derived hematopoietic cells originally expressed higher levels of MCM2 than BALB/c cells and exhibited more frequent apoptosis after DNA-damage by doxorubicin when the cells expressed the Friend leukemia virus envelope protein gp70. Transduction and immunoprecipitation assays using various deletion mutants of
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Report
(4 results)
Research Products
(71 results)
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[Journal Article] Differential expression of Toll-like receptors infollicular lymphoma, diffuse large B-cell lymphomaand peripheral T-cell lymphoma2010
Author(s)
Smith TJ, Yamamoto K, Kurata M, Yukimori A, SuzukiS, Umeda S, Sugawara E, Kojima Y, Sawabe M, Nakagawa Y, Suzuki K, Crawley JTB, Kitagawa M
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Journal Title
Exp Mol Pathol
Volume: 89
Pages: 284-290
Related Report
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[Journal Article] Analysis of sixteen cases of chronic hypersensitivity pneumonitis and comparison withidiopathic pulmonary fibrosis/usual interstitial pneumonia2009
Author(s)
Akashi T, Takemura T, Ando N, Eishi Y, Kitagawa M, Takizawa T, Koike M, Igari T, Kawachi H, KobayashiD, Ito T, Kumagai J, Tanabe H, Ito T, Tamahashi U, Tsugata M, Chiba T, Hirooka S, Endo T, Kurata M, Yamamoto K, Warabi M, Tsunemi A, Kuroiwa T, Kayamori K
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Journal Title
Am J Clin Pathol
Volume: 131
Pages: 405-415
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