Analyses of phenotypic changes of Hodgkin and Reed-Stemberg cells to anaplastic large cell lymphoma cells by p80.
| 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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Report
(3 results)
Research Products
(21 results)
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[Journal Article] Dual targeting of transformed and untransformed HTLV-1-infected T cells by DHMEQ, a potent and selective inhibitor of NF-{kappa}B, as a strategy for chemoprevention and therapy of adult T-cell leukemia.2005
Author(s)
Watanabe M, Ohsugi T, Shoda M, Ishida T, Aizawa S, Maruyama-Nagai M, Utsunomiya A, Koga S, Yamada Y, Kamihira S, Okayama A, Kikuchi H, Uozumi K, Yamaguchi K, Higashihara M, Umezawa K, Watanabe T, Horie R.
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Journal Title
Blood 106
Pages: 2462-2471
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] A novel NF-kB inhibitor DHMEQ selectively targets constitutive NF-kB activity and induces apoptosis of multiple myeloma cells in vitro and in vivo.2005
Author(s)
Watanabe M, Dewan MZ, Okamura T, Sasaki M, Itoh K, Higashihara M, Mizoguchi H, Honda M, Sata T, Watanabe T, Yamamoto N, Umezawa K, Horie R.
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Journal Title
Int J Cancer. 114
Pages: 32-38
Description
「研究成果報告書概要(欧文)」より
Related Report
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