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Analyses of molecular bases of Hodgkin lymphoma by CD30-NF-kB pathway.

Research Project

Project/Area Number 14570162
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionKITASATO UNIVERSITY

Principal Investigator

HORIE Ryouichi  Kitasato University, School of Medicine, Assistant Prof., 医学部, 講師 (80229228)

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)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
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)
KeywordsHodgkin's lymphoma / Hodgkin and Reed-Sternberg cells / CD30 / NF-κB / CD30 promoter / JunB / NF-κB / IL-13 / TRAF / NIK / IKK / signalosome
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.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Horie R, Watanabe M, Ishida T et al.: "The NPM-ALK oncoprotein abrogates CD30 signaling and constitutive NF-kB activation in anaplastic large cell lymphoma."Cancer Cell. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Horie R, Watanabe T.: "The biological basis of Hodgkin's lymphpoma."Drug News Perspect.. 16. 649-656 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Watanabe M, Ogawa Y, Ito K, et al.: "AP-1 mediated relief of repressive activity of the CD30 promoter microsatellite in Hodgkin and Reed-Sternberg cells"Am J Pathol. 163. 633-641 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Horie R, Higashihara M, Watanabe T.: "The biology of Hodgkin's lymphpoma and CD30 signal transduction."Int J Hematol. 77. 37-47 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Horie R, Watanabe T, Ito K et al.: "Cytoplasmic aggregation of TRAF2 and TRAF5 proteins in Hodgkin's and Reed-Sternberg cells."Am J Pathol. 160. 1647-1654 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Horie R, Ito K, Morisita Y et al.: "Ligand independent signaling by overexpressed CD30 drives NF-kB activation in Hodgkin and Reed-Sternberg cells."Oncogene. 21. 2493-2503 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Horie R, Watanabe M, Ishida T, Koiwa T, Aizawa S, Itoh K, Higashihara M, Kadin ME, Watanahe T: "The NPM-ALK oncoprotein abrogates CD30 signaling and constitutive NF-κB activation in anaplastic large cell lymphoma."Cancer Cell. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Horie R, Watanabe T: "The biological basis of Hodgkin's lymphoma."Drug News Perspect. 16. 649-659 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Watanabe M, Ogawa Y, Ito K, Higashihara M, Kadin ME, Watanabe T, Horie R: "AP-1 mediated relief of repressive activity of the CD30 promoter microsatellite in Hodgkin and Reed-Sternberg cells"Am J Pathol. 163. 633-641 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Horie R, Higashihara M, Watanabe T: "The biology of Hodgkin's lymphoma and CD30 signal transduction."Int J Hematol. 77. 37-47 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Watanabe T, Ito K, Morisita Y, Watanabe M, Higashihara M, Kadin M, Watanabe T: "Cytoplasmic aggregation of TRAF2 and TRAF5 proteins in Hodgkin's and Reed-Sternberg cells."Am J Pathol. 160. 1647-1654 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Horie R, Ito K, Morisita Y, Watanabe M, Higashihara M, Kadin M, Watanabe.T: "Ligand independent signaling by overexpresse CD30 drives NF-kB activation in Hodgkin and Reed-Sternberg cells."Oncogene. 21. 2493-2503 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Horie R, Watanabe M, Ishida T et al.: "The NPM-ALK oncoprotein abrogates CD3O signaling and constitutive NF-κB activation in anaplastic large cell lymphoma."Cancer Cell. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Horie R, Watanabe T: "The biological basis of Hodgkin's lymphpoma."Drug News Perspect.. 16. 649-656 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Watanabe M, Ogawa Y, Ito K, et al.: "AP-1 mediated relief of repressive activity of the CD30 promoter microsatellite in Hodgkin and Reed-Sternberg cells"Am J Pathol. 163. 633-641 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Horie R, Higashihara M, Watanabe T: "The biology of Hodgkin's lymphpoma and CD30 signal transduction."Int J Hematol. 77. 37-47 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Horie R, Watanabe T, Ito K et al.: "Cytoplasmic aggregation of TRAF2 and TRAF5 proteins in Hodgkin's and Reed-Sternberg cells."Am J Pathol. 160. 1647-1654 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Horie R, Ito K, Morisita Y et al.: "Ligand independent signaling by overexpressed CD30 drives NF-kB activation in Hodgkin and Reed-Sternberg cells."Oncogene. 21. 2493-2503 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Horie R, Higashihara M, Watanabe T: "The biology of Hodgkin's lymphpoma and CD30 signal transduction"Int J Hematol. 77. 37-47 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hore R, Watanabe T, Ito K et al.: "Cytoplasmic aggregation of TRAF2 and TRAF5 proteins in Hodgkin's and Reed-Sternberg cells. 160:1647-1654.2002"Am J Pathol. 160. 1647-1654 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Horie R, Ito K, Morisita Y et al.: "Ligand independent signaling by overexpressed CD30 drives NF-κB activation in Hodgkin and Reed-Sternberg cells"Oncogene. 21. 2493-2503 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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