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Molecular analysis of malignant lymphoma-related oncogenes and its clinical application for diagnosis and treatment.

Research Project

Project/Area Number 15591034
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionAichi Cancer Center

Principal Investigator

HOSOKAWA Yoshitaka  Aichi Cancer Center, Div.Molecular Medicine, Section Head, 遺伝子医療研究部, 室長 (60229193)

Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsMalignant lymphoma / apoptosis / Chromosome translocation / プロテオミックス / NF-κB
Research Abstract

1)API2-MALT1. t(11;18)(q21;q21) is a characteristic chromosomal translocation in mucosa-associated lymphoid tissue(MALT) type lymphoma, and this translocation results in chimeric transcript of API2(APoptosis Inhibitor 2,also known as c-IAP2)-MALT1(Mucosa-Associated Lymphoma Translocation gene 1). To identify proteins that bind API2-MALT1 chimeric protein, we employed coimmunoprecipitation and SDS PAGE analysis, followed by liquid chromatography-electrospray ionization tandem mass spectrometry. As a result, Smac, Htra2,and TRAF2 were identified as API2-MALT1-binding proteins. Immunoprecipitation analysis demonstrated that ectopically expressed API2-MALT1 protein indeed binds to these endogeneous proteins. Furthermore, API2-MALT1 protein significantly inhibited Smac-promoted apoptosis in UV irradiated HeLa cells. These data strongly suggest that API2-MALT1 can block apoptosis, at least in part, by inhibiting Smac-mediated apoptotic pathway.
2)BCL6. The BCL-6/LAZ3 gene encodes a zinc-finge … More r transcriptional represser and is located at the breakpoint of the 3q27-associated translations that occur most frequently in non-Hodgkin's lymphomas (NHLs To examine cell responses and target genes related to the BCL-6 signaling pathway, we established Ba/F3 pro-B cells carrrying a human BCL-6 transgene that is inducible under control of the lactose operon. Using a cDNAarray hybridization technique, we found that the induced BCL-6 protein can downregulate the expressions of the genes, cyclin A2. chemokine receptor CXCR4,and insulin-like growth factor binding protein-4(IGFBP-4) in the Ba/F3 cells. Northern blot analysis established that the expressions of these genes were indeed downregulated by the induced BCL-6 protein but in a somewhat different manner. The induced BCL-6 protein also inhibited cell proliferation of Ba/F3 cells. These findings strongly suggest that three key genes, namely cyclin A2,CXCR4 and IGFBP-4 may play a role in the downstream of the BCL-6 signaling pathway during B-lymphoid differentiation. Less

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (21 results)

All 2005 2004 2003 Other

All Journal Article (16 results) Publications (5 results)

  • [Journal Article] Anti-apoptotic action of API2-MALT1 fusion protein involved in t(11;18)(q21;q21) MALT lymphoma.2005

    • Author(s)
      Hosokawa Y et al.
    • Journal Title

      Apoptosis 10

      Pages: 25-34

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Anti-apoptotic action of API2-MALT1 fusion protein involved in t(11;18)(q21;q21) MALT lymphoma.2005

    • Author(s)
      Hosokawa Y.
    • Journal Title

      Review Article Apoptosis 10

      Pages: 25-34

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] MASL1, a candidate oncogene found in amplication at 8p23.1, is translocated in immunoblastic B-cell lymphoma cell line OCI-LY8.2004

    • Author(s)
      Tagawa H et al.
    • Journal Title

      Oncogene 23

      Pages: 2576-2581

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Anti-apoptotic function of API2-MALT1 fusion protein involved in t(11;18)(q21;q21) MALT lymphoma.2004

    • Author(s)
      Hosokawa Y et al.
    • Journal Title

      Cancer Research 64

      Pages: 3452-3457

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] NF-kB activation and anti-apoptosis in MALT lymphoma.2004

    • Author(s)
      Hosokawa Y et al.
    • Journal Title

      Int.J.Heamatol. 80

      Pages: 215-223

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] MASL1,a candidate oncogene found in amplication at 8p23.1,is translocated in immunoblastic B-cell lymphoma cell line OCI-LY8.2004

    • Author(s)
      Tagawa H., Karnan S, Kasugai Y, Tuzuki S, Suzuki R, Hosokawa Y, Seto M.
    • Journal Title

      Oncogene 23

      Pages: 2576-2581

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Anti-apoptotic function of API2-MALT1 fusion protein involved in t(11;18)(q21;q21) MALT lymphoma.2004

    • Author(s)
      Hosokawa Y, Suzuki H, Suzuki Y, Takahashi R, Seto M.
    • Journal Title

      Cancer Research 64

      Pages: 3452-3457

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Comparison of genetic aberrations in CD10(+) diffused large B-cell lymphoma and follicular lymphoma by comparative genomic hybridization and tissue-fluorescence in situ hybridization.2004

    • Author(s)
      Zhang X, Karnan S, Tagawa H, Suzuki R, Tsuzuki S, Hosokawa Y, Morishima Y, Nakamura S, Seto M.
    • Journal Title

      Cancer Sci. 95

      Pages: 809-814

    • NAID

      10014170490

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] NF-kB activation and anti-apoptosis in MALT lymphoma.2004

    • Author(s)
      Hosokawa Y, Seto M.
    • Journal Title

      Progress in Hematology Review Article Int.J.Heamatol. 80

      Pages: 215-223

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Stability and subcellular localization of API2-MAIT1 chimeric protein involved in t(11;18)(q21;q21) MALT lymphoma2003

    • Author(s)
      Izumiyama K et al.
    • Journal Title

      Oncogene 22

      Pages: 8085-8092

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Heterogeneous copy number of API2-MALT1 chimeric transcripts mucosa-associated lymphoid tissue lymphoma.2003

    • Author(s)
      Suguro-Katayama M et al.
    • Journal Title

      Leukemia 17

      Pages: 2508-2512

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mutational analysis of the ST7 gene in human myeloid tumor cell lines.2003

    • Author(s)
      Sivasundaram K, Suzuki H, Seto M, Hosokawa Y.
    • Journal Title

      Oncology Reports 10

      Pages: 1737-1739

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Stability and subcellular localization of API2-MALT1 chimeric protein involved in t(11;18)(q21;q21) MALT lymphoma.2003

    • Author(s)
      Izumiyama K, Nakagawa M, Yonezumi M, Kasugai K, Suzuki R, Suzuki H, Tsuzuki S, Hosokawa Y, Asaka M, Seto M.
    • Journal Title

      Oncogene 22

      Pages: 8085-8092

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Heterogeneous copy number of API2-MALT1 chimeric transcripts in mucosa-associated lymphoid tissue lymphoma.2003

    • Author(s)
      Suguro-Katayama M, Suzuki R, Kasugai Y, Nakamura T, Suzuki H, Hosokawa Y, Shiku H, Nakamura S, Seto M.
    • Journal Title

      Leukemia 17

      Pages: 2508-2512

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Stability and subcellular localization of API2-MALT1 chimeric protein involved in t(11;18)(q21;q21) MALT lymphoma2003

    • Author(s)
      Izumiyama K et al.
    • Journal Title

      Oncogene 22

      Pages: 8085-8092

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Heterogeneous copy number of API2-MALT1 chimeric transcripts in mucosa-associated lymphoid tissue lymphoma.2003

    • Author(s)
      Suguro-Katayama M et al.
    • Journal Title

      Leukemia 17

      Pages: 2508-2512

    • Related Report
      2004 Annual Research Report
  • [Publications] Sivasundaram K et al.: "Mutational analysis of the ST7 gene in human myeloid tumor cell lines."Oncology Reports. 10. 1737-1739 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Izumiyama K et al.: "Stability and subcellular localization of API2-MALT1 chimeric protein involved in t(11;18)(q21;q21) MALT lymphoma."Oncogene. 22. 8085-8092 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Suguro-Katayama M et al.: "Heterogeneous copy number of API2-MALT1 chimeric transcripts in mucosa-associated lymphoid tissue lymphoma."Leukemia. 17. 2508-2512 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tagawa H.et al.: "MASL1,a candidate oncogene found in amplication at 8p23.1,is translocated in immunoblastic B-cell lymphoma cell line OCI-LY8."Oncogene. in press.

    • Related Report
      2003 Annual Research Report
  • [Publications] Hosokawa Y et al.: "Anti-apoptotic function of API2-MALT1 fusion protein involved in t(11;18)(q21;q21) MALT lymphoma."Cancer Research. in press.

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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