| Project/Area Number |
16590294
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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 |
Human pathology
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| Research Institution | KITASATO UNIVERSITY |
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Principal Investigator |
HORIE Ryouichi KITASATO UNIVERSITY, School of Medi., Associate Prof., 医学部, 助教授 (80229228)
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| Co-Investigator(Kenkyū-buntansha) |
HIGASHIHARA Masaaki KITASATO UNIVERSITY, School of Medi., Prof., 医学部, 教授 (80165084)
WATANABE Toshiki Tokyo Univ., Inst Med.Sci., Associate Prof., 医科学研究所, 助教授 (30182934)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Hodgkin lymphoma / ALCL / NF-κB / NPM-ALK / JunB / CD30 / Hogkinリンパ腫 / 未分化大細胞性リンパ腫 / Nf-kB / P80 |
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| Research Abstract |
Overexpression of CD30 and constitutive NF-κB activation characterizes tumor cells of classic Hodgkin lymphoma (HL), Hodgkin and Reed-Sternberg (H-RS) cells. NPM-ALK characterizes anaplastic large cell lymphoma (ALCL), as does the high expression of CD30, a feature shared with H-RS cells of classic HL. In H-RS cells, ligand-independent signaling by overexpressed CD30 drives constitutive NF-κB activation, which is absent in ALCL cells. We show that NPM-ALK impedes CD30 signaling and NF-κB activation, dependent on both ALK kinase activity and the N-terminal NPM domain. NPM-ALK transduction into H-RS cell lines abrogates recruitment and aggregation of TRAF proteins, inducing an ALCL-like morphology and phenotype. TRAF2 associates. with NPM-ALK at a consensus binding motif located in the kinase domain. Thus, NPM-ALK abrogates CD30-driven NF-κB activation and can also induce an ALCL phenotype, distinguishing ALCL cells from H-RS cells of T cell origin. We also analyzed the mechanism of CD30 overexpression in H-RS cells and ALCL cells. JunB is overexpressed in both H-RS cells and ALCL cells and is involeved in CD30 overexpression, suggesting the common mechanism of CD30 overexpression in H-RS cells and ALCL cells.
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