| Project/Area Number |
14570162
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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 Medicine, Assistant Prof., 医学部, 講師 (80229228)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Toshiki Inst. Med. Sci. Tokyo University, Associated Prof., 医科学研究所, 助教授 (30182934)
HIGASHIHARA Masaaki Kitasato University, School of Medicine, Prof., 医学部, 教授 (80165084)
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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 |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Hodgkin's lymphoma / Hodgkin and Reed-Sternberg cells / CD30 / NF-κB / CD30 promoter / JunB / NF-κB / IL-13 / TRAF / NIK / IKK / signalosome |
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| Research Abstract |
Overexpression of CD30 and constitutive NF-κB activation characterizes tumor cells of Hodgkin's lymphoma (HL), Hodgkin and Reed-Sternberg (H-RS) cells. We report that in H-RS cells overexpression of CD30 leads to self-aggregation, recruitment of TRAF2 and TRAF5, and NF-κB activation, independent of CD30 ligand. CD30 and TRAF proteins co-localized in H-RS cell lines and in lymph nodes of HL.
We identified TRAF protein aggregation in the cytoplasm of H-RS cells and also showed the involvement of TRAF protein aggregation in the signaling process of CD30. Thus, cytoplasmic aggregation of TRAF proteins appears to reflect constitutive CD30 signaling which is characteristic to H-RS cells.
We structurally and functionally characterized the CD30 promoter, and identified JunB as a molecule that is involved in CD30 overexpression in H-RS cells.
Our results give us a key to understand molecules involved in the transformation of germinal center B cells to H-RS cells in view of Jung-CD30-NF-κB loop.
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