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Biological role of the regulation of the expressions of transpersonal DNA polymereases by hypoxia

Research Project

Project/Area Number 16590257
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionChiba Cancer Center Research Institute

Principal Investigator

TAKENAGA Keizo  Chiba Cancer Center Research Institute, Division of Chemotherapy, Senior Investigator, 化学療法研究部, 主席研究員 (80260256)

Co-Investigator(Kenkyū-buntansha) KOSHIKAWA Nobuko  Chiba Cancer Center Research Institute, Division of Pathology, Senior Investigator, 化学療法研究部, 主席研究員 (90260249)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsHypoxia / Mutation / HIF-1 / Translesional DNA polymerase / DNA polymerase ι
Research Abstract

AIM : It has been demonstrated that hypoxia/reoxygenation increases mutation frequency in tumor cells, leading to genetic instability. However, its molecular mechanism remains to be obscure. It is known that a large amount of reactive oxygen species is produced in cells after hypoxia/reoxygenation which generate highly mutagenic base 8-oxoG. In this study, we evaluated the possible involvement of error-prone DNA polymerases that can bypass 8-oxoG and proceed translesional DNA replication in hypoxia/reoxygenation-induced mutagenesis. RESULTS : The expressions of error-prone DNA polymerases,η,ι,κ and μ, in HeLa cells were examined by RT-PCR after culturing them under hypoxic conditions (1% O_2) for 6-24 h. The results showed that the expression of DNA polymerase ι (pol ι) gene was significantly up-regulated by hypoxia. Hypoxia mimetic desferrioxamine and CoCl_2 also increased the expression of pol ι gene. Hypoxia up-regulated the pol ι gene in all of 8 human cell lines examined. Luciferase reporter assays revealed that the transcriptional activity of the pol ι gene promoter region (-1345/+419) was increased in response to hypoxia and constitutive active HIF-1 α and that the activity was suppressed by dominant negative HIF-1 α. Furthermore, gel shift and chromatin immunoprecipitation assays demonstrated the importance of the ACGTG sequence in the intron 1 of pol ι gene for HIF-1 responsiveness. On the other hand, it was found that the frequency of mutation was increased in MCF7 cells by hypoxia/reoxygenation, but it was suppressed by treatment of the cells with pol ι -specific small interfering RNA. CONCLUSION : The results suggest that Pol ι is involved in the hypoxia/reoxygenation-induced mutagenesis.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (21 results)

All 2006 2005

All Journal Article (21 results)

  • [Journal Article] Hypoxia selects for high-metastatic Lewis lung caecinoma cells overexpressing Mcl-1 and exhibiting reduced apoptotic potential in solid tumors.2006

    • Author(s)
      N.Koshikawa
    • Journal Title

      Oncpgene 25

      Pages: 917-928

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Role of intracellular S100A4 for migration of rat astrocytes.2006

    • Author(s)
      K.Takenaga
    • Journal Title

      Glia 53

      Pages: 313-321

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Sensory neurite outgrowth on white matter astrocytes is influenced by intracellular and extracellular S100A4 protein2006

    • Author(s)
      Z.Fang
    • Journal Title

      J. Neurosci. Res 83

      Pages: 619-626

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A procedure for culturing astrocytes from white matter and the application of the siRNA technique for silencing the expression of their specific marker. S100A4.2006

    • Author(s)
      EN.Kozlova
    • Journal Title

      Brain Res Brain Res Protoc 15

      Pages: 59-65

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Intracallular calcium-binding protein A100A4 influences injury-induced migration of white matter astrocytes.2006

    • Author(s)
      EN.Kozlova
    • Journal Title

      Acta Neuropathol.(Berl) 111

      Pages: 213-219

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hypoxia selects for high-metastatic Lewis lung carcinoma cells overexpressing Mcl-1 and exhibiting reduced apoptotic potential in solid tumors.2006

    • Author(s)
      N.Koshikawa, et al.
    • Journal Title

      Oncogene 25

      Pages: 917-928

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Role of intracellular S 100A4 formigration of rat astrocytes.2006

    • Author(s)
      K.Takenaga, et al.
    • Journal Title

      Glia 53

      Pages: 313-321

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Sensory neurite outgrowth on whitematter astrocytes is influenced by intracellular and extracellular S100A4 protein.2006

    • Author(s)
      Z.Fang, et al.
    • Journal Title

      J.Neurosci.Res. 83

      Pages: 619-626

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A procedure for culturing astrocytesfrom white matter and the application of the siRNA technique for silencing the expression of their specificmarker, S 100A4.2006

    • Author(s)
      EN.Kozlova, et al.
    • Journal Title

      Brain Res Brain Res Protoc. 15

      Pages: 59-65

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Intracellular calcium-binding protein S 100A4 influences injury-induced migration of whitematter astrocytes.2006

    • Author(s)
      Z.Fang, et al.
    • Journal Title

      Acta Neuropathol.(Berl). 111

      Pages: 213-219

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hypoxia selects for high-metastatic Lewis lung carcinoma cells overexpressing Mcl-1 and exhibiting reduced apoptotic potential in solid tumors.2006

    • Author(s)
      Koshikawa N, Takenaga K. et al.
    • Journal Title

      Oncogene 25

      Pages: 917-928

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Role of intracellular S100A4 for migration of rat astrocytes.2006

    • Author(s)
      Takenaga K, Kozlova EN
    • Journal Title

      Glia 53

      Pages: 313-321

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Sensory neurite outgrowth on white matter astrocytes is influenced by intracellular and extracellular S100A4 protein.2006

    • Author(s)
      Fang Z, Forslund N, Takenaga K, et al.
    • Journal Title

      J Neurosci Res. (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Intracellular calcium-binding protein S100A4 influences injury-induced migration of white matter astrocytes.2006

    • Author(s)
      Fang Z, Takenaga K, et al.
    • Journal Title

      Acta Neuropathol (Berl). (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Hypoxia-regulated expression of attenuated diphtheria toxin A fused with hypoxia-inducible factor-1 α oxygen-dependent degradation domain preferentially indeces spoptosis of hypoxic cells in solid tumor.2005

    • Author(s)
      N.Koshikawa
    • Journal Title

      Cancer Research 65

      Pages: 11622-11630

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] S100A4 inhibition by RNAi up-regulates osteoblast related genes in periodontal ligament calls. Biochem.2005

    • Author(s)
      C.Kato
    • Journal Title

      Biochem. Biophys. Res. Commun 326

      Pages: 147-153

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hypoxia-regulated expression of attenuated diphtheria toxin A fused with hypoxia- inducible factor-1 α oxygen-dependent degradation domain preferentially induces apoptosis of hypoxic cells in solid tumor.2005

    • Author(s)
      N.Koshikawa, et al.
    • Journal Title

      Cancer Research. 65

      Pages: 11622-11630

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] S100A4 inhibition by RNAi up-regulates osteoblast related genes in periodontal ligament cells.2005

    • Author(s)
      C.Kato, et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 326

      Pages: 147-153

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A Calcium binding protein, S 100A4,mediates T cell dependent cytotoxicity as atransformation-associated antigen.2005

    • Author(s)
      N.Kondo, et al.
    • Journal Title

      Microbiol.Immunol. 49

      Pages: 49-56

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hypoxia-regulated expression of attenuated diphtheria toxin A fused with hypoxia-inducible factor-1 α oxygen-dependent degradation domain preferentially induces apoptosis of hypoxic cells in solid tumor.2005

    • Author(s)
      Koshikawa N, Takenaga K.
    • Journal Title

      Cancer Res. 65

      Pages: 11622-11630

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A procedure for culturing astrocytes from white matter and the application of the siRNA technique for silencing the expression of their specific marker, S100A4.2005

    • Author(s)
      Kozlova EN, Takenaga K.
    • Journal Title

      Brain Res Brain Res Protoc. 15

      Pages: 59-65

    • Related Report
      2005 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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