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Enhancement of radiation-induced apoptosis by retroviral infection : implication for the gene therapy

Research Project

Project/Area Number 14570180
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

KITAGAWA Masanobu  Tokyo Medical and Dental University, Graduate School, Department of Comprehensive Pathology, Associate Professor, 大学院・医歯学総合研究科, 助教授 (10177834)

Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordsretrovirus / DNA damage / apoptosis / p53 / DNA-PK / フレンド白血病ウイルス / ATM
Research Abstract

We established the experimental system using C3H mice indicating that retroviral infection remarkably enhanced the radiation-induced apoptosis. FLU-infected C3H mice exhibited lethal anemia after low dose total body irradiation (3 Gy) caused by apoptosis of hematopoietic cells of the bone marrow. The enhancement of apoptosis was p53-dependent and regulated by PI3-kinases, DNA-dependent protein kinase (DNA-PK) and ataxia telangiectasia mutation kinase (ATM). In general, ATM kinase plays a role in the activation of p53 after DNA damage like irradiation. However, in this study, we could clarify that the DNA-PK bound with the FLV-derived gp70 and introduced marked activation (phosphorylation) of p53. For this activation of DNA-PK, a host gene product seemed essential in association with gp70.
Using in vitro cell line systems, we confirmed the enhancement of radiation-induced apoptosis by infection with FLV. Acute myelogenous leukemia cell lines established from radiation-induced leukemia cells of C3H mice were used for the study. These cell lines had normal but not mutated p53. Viral infection was confirmed by the expression of viral gp70 on the cell surface. Now we are investigating about the mechanisms of DNA-PK activation by viral gp70.
This model would be useful for establishing the therapeutic system by the specific induction of apoptosis to abnormal cells such as cancers by using gp70 and low dose irradiation.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (24 results)

All 2004 Other

All Journal Article (14 results) Publications (10 results)

  • [Journal Article] Differential expression of survivin in bone marrow cells from patients with acute lymphocytic leukemia and chronic lymphocytic leukemia.2004

    • Author(s)
      Nakagawa Y, Yamaguchi S.Hasegawa M, Nemoto T, Inoue M, Suzuki K, Hirokawa K, Kitagawa M.
    • Journal Title

      Leukemia Research 28

      Pages: 487-494

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of IAP family proteins in myelodysplastic syndromes transforming to overt leukemia.2004

    • Author(s)
      Yamamoto K, Abe S, Nakagawa Y, Suzuki K, Hasegawa M Inoue H, Kurata M, Hirokawa K, Kitagawa M
    • Journal Title

      Leukemia Research 28

      Pages: 1203-1211

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression level of Wnt signaling components possibly influence the behavior of colorectal cancer in different age groups.2004

    • Author(s)
      Seidler HBK, Utsuyama M, Nagaoka S.Takemura T.Kitagawa M, Hirokawa K.
    • Journal Title

      Experimental and Molecular Pathology 76

      Pages: 224-233

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of IAP family proteins in esophageal cancer2004

    • Author(s)
      Nemoto T, Kitagawa M.Hasegawa M, Akashi T, Takizawa T, Hirokawa K, Koike M.
    • Journal Title

      Experimental and Molecular Pathology 76

      Pages: 253-259

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of IAP family proteins in colorectal cancer in different age groups.2004

    • Author(s)
      Endo T, Abe S, Seidler HBK, Nagaoka S, Takemura T, Utsuyama M, Kitagawa M, Hirokawa K.
    • Journal Title

      Cancer Immunology and Immunotherapy 53

      Pages: 770-776

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cytological basis for enhancement of radiation-induced mortality by Friend leukaemia virus infection.2004

    • Author(s)
      Tanaka K, Watanabe K, Yamaguchi S.Hasegawa M, Kitagawa M. Aizawa S.
    • Journal Title

      International Journal of Radiation Biology 80

      Pages: 673-681

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Differential expression of survivin in bone marrow cells from patients with acute lymphocytic leukemia and chronic lymphocytic leukemia.2004

    • Author(s)
      Nakagawa Y, Yamaguchi S, Hasegawa M, Nemoto T, Inoue M, Suzuki K, Hirokawa K, Kitagawa M.
    • Journal Title

      Leukemia Research 28

      Pages: 487-494

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression of IAP family proteins in myelodysplastic syndromes transforming to overt leukemia.2004

    • Author(s)
      Yamamoto K, Abe S, Nakagawa Y, Suzuki K, Hasegawa M, Inoue M, Kurata M, Hirokawa K, Kitagawa M.
    • Journal Title

      Leukemia Research 28

      Pages: 1203-1211

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Expression level of Wnt signaling components possibly influence the behavior of colorectal cancer in different age groups.2004

    • Author(s)
      Seidler HBK, Utsuyama M, Nagaoka S, Takemura T, Kitagawa M, Hirokawa K.
    • Journal Title

      Experimental and Molecular Pathology 76

      Pages: 224-233

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Expression of IAP family proteins in esophageal cancer.2004

    • Author(s)
      Nemoto T, Kitagawa M, Hasegawa M, Akashi T, Takizawa T, Hirokawa K, Koike M.
    • Journal Title

      Experimental and Molecular Pathology 76

      Pages: 253-259

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Cytological basis for enhancement of radiation-induced mortality by Friend leukaemia virus infection.2004

    • Author(s)
      Tanaka K, Watanabe K, Yamaguchi S, Hasegawa M, Kitagawa M, Aizawa S.
    • Journal Title

      International Journal of Radiation Biology 80

      Pages: 673-681

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Differential expression of survivin in bone marrow cells from patients with cute lymphocytic leukemia and chronic lymphocytic leukemia.2004

    • Author(s)
      Nakagawa Y., Yamaguchi S., Hasegewa M., Nomote T., Inoue M., Suzuki K., Hirokawa K., Kitagawa M.
    • Journal Title

      Leukemia Research 28

      Pages: 487-494

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expression of IAP family proteins in myelodysplastic syndromes transforming to overt leukemia.2004

    • Author(s)
      Yamamote K., Abe S., Nakagawa Y., Suzuki K., Hasegewa M., Kurata M., Hirokawa K., Kitagawa M.
    • Journal Title

      Leukemia Research 28

      Pages: 1203-1211

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expression of LAP family proteins in colorectal cancer in different age groups.2004

    • Author(s)
      Endo T, Abe S, Scidler HBK, Nagaoka S, Takemura T, Utsuyama M, Kitagawa M, Hirokawa K.
    • Journal Title

      Cancer Immunology and Immunotherapy 53

      Pages: 770-776

    • Related Report
      2004 Annual Research Report
  • [Publications] Seidler HBK, Utsuyama M, Nagaoka S, Takemura T, Kitagawa M, Hirokawa K.: "Expression level of Wnt signaling components possibly influence the behavior of colorectal cancer in different age groups."Experimental and Molecular Pathology. (in press). (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakagawa Y, Ymaguchi S, Hasegawa M, Nemoto T, Inoue M, Suzuki K, Hirokawa K, Kitagawa M.: "Differential expression of survivin in bone marrow cells from patients with acute lymphocytic leukemia and chronic lymphocytic leukemia."Leukemia Research. (in press). (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fujisaki C, Utsuyama M, Kuroda Y, Watanabe A, Seidler H, Watanabe S, Kitagawa M, Hirokawa K.: "An immunosuppressive drug, cyclosporin-A acts like anti-depressant for rats under unpredictable chronic stress."Journal of Medical and Dental Sciences. 50. 93-100 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nagaoka S, Shiraishi J, Utsuyama M, Seki S, Takemura T, Kitagawa M, Sawabe M, Takubo K, Hirokawa K.: "Poor prognosis of colorectal cancer in patients over 80 years old is associated with down-regulation of tumor suppressor genes."Journal of Clinical Gastroenterology. 37. 48-54 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sawanobori M, Yaraaguchi S, Hasegawa M, Inoue M, Suzuki K, Kamiyama R, Hirokawa K, Kitagawa M.: "Expression of TNF receptors and related signaling molecules in the bone marrow from patients with myelodysplastic syndromes."Leukemia Research. 27. 583-591 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamaguchi S, Hasegawa M, Suzuki T, Ikeda H, Aizawa S, Hirokawa K, Kitagawa M.: "In vivo distribution of receptor for ecotropic murine leukemia virus and binding envelope protein of Friend Murine leukemia virus."Archives of Virology. 148. 1175-1184 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kitagawa M, et al.: "Friend leukemia virus infection enhances DNA damage-induced apoptosis of hematopoietic cells, causing lethal anemia in C3H host"Journal of Virology. Vol.76. 7790-7798 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tanaka K, Kitagawa M, et al.: "Incidence of apoptosis increases with age in colorectal cancer"Experimental Gerontology. Vol.37. 1469-1487 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamaguchi S, Kitagawa M, et al.: "In vivo distribution of receptor for ecotropic murine leukemia virus and Binding of envelope protein of Friend leukemia virus"Archives of Virology. (in press). (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sawanobori M, Kitagawa M, et al.: "Expression of TNF receptors and related signaling molecules in the bone marrow from patients with myelodysplastic syndromes"Leukemia Research. (in press). (2002)

    • Related Report
      2002 Annual Research Report

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

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