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Analysis of stress defense mechanism against oral cancer by using A170 gene knockout mouse

Research Project

Project/Area Number 11470429
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionUniversity of Tsukuba

Principal Investigator

YOSHIDA Hiroshi  Univ. of Tsukuba, Inst. Of Clinical medicine, professor, 臨床医学系, 教授 (80014330)

Co-Investigator(Kenkyū-buntansha) YUSA Hiroshi  Univ. of Tsukuba, Inst.of Clinical medicine, instructor, 臨床医学系, 助手 (40292560)
ONIZAWA Kojiro  Univ. of Tsukuba, Inst.of Clinical medicine, assistant professor, 臨床医学系, 講師 (60194578)
ISHII Tetsuro  Univ. of Tsukuba, Inst.of Basic medicine, associate professor, 基礎医学系, 助教授 (20111370)
YANAGAWA Toru  Univ. of Tsukuba, Inst.of Clinical medicine, assistant professor, 臨床医学系, 講師 (10312852)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2001: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2000: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 1999: ¥5,200,000 (Direct Cost: ¥5,200,000)
KeywordsA170 / zeta interacting protein / gene targeting / oxidative stress / stress response / zeta interacting protein (ZIP) / gene targetting / zeta interacting protein(ZIP)
Research Abstract

In this study we focused on the oxidative stress protein A170 which was estimated to play a important role in oral and maxillofacial lesions because it was associated with the oncogene and osteoblast differentiation. We planed 1) to construct A170 gene knockout mouse and 2) to analyze the stress : response of the oxidative stress proteins including A170 from clinical and basic viewpoints.
1) About knockout mouse construction we carried out the following procedures. We isolated the genomic clone and characterized the gene of A170 from BAC/129Sv mouse genome library. After mapping we designed the A170-null targeting vector. The modified gene with the vector was introduced into the ES cells by electroporation. Genetically altered cells were injected into embryonic blastocysts derived from C57/B6N and then implanted into a surrogate mother. Chimeras were generated with a high agouti percentage coat which indicated acceptance of the gene mutation. These chimeric mice were then mated with CS7/B6 mice. The F1 offspring containing the agouti coat indicated germline transmission. The germline transmission was confirmed by FCR. Finally we mated Flmouse and knock out mouse (F2) construction was completed.
2) While knockout mouse construction we investigated the induction of A170 by stress agents using the rat. We also investigated Peroxiredoxin I (Prx I = MSP23) and the other stress inducible protein expression as a foundation for A170 knockout-mouse analysis. Moreover, we also investigated the expression level of oral cancer from clinical samples.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Nakaso K.: "Effects of kainate-mediated excitotoxicity on the expression of rat counterparts of A170 and MSP23 stress proteins in the brain"Brain Res Mol Brain Res. 69(2). 155-163 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ishii T.: "Oxidative stress-inducible proteins in macrophages"Free Radic Res. 31(4). 351-355 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yanagawa T.: "c-Abl expression in oral squamous cell carcinomas"Oral Oncol. 36(1). 89-94 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakaso K: "Oxidative stress-related proteins A170 and heme oxygenase-1 are differently induced in the rat cerebellum under kainate-mediated excitotoxicity"Neurosci Lett. 282(1-2). 57-60 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ishii T.: "Induction of murine intestinal and hepatic peroxiredoxin MSP23 by dietary butylated hydroxyanisole"Carcinogenesis. 21(5). 1013-1016 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yanagawa T: "Peroxiredoxin I expression in oral cancer : a potential new tumor marker"Cancer Lett. 156(1). 27-35 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakaso K, et al.: "Effects of kainate-mediated excitotoxicity on the expression of rat counterparts of A170 and MSP23 stress proteins in the brain"Brain Res Mol Brain Res. 69 (2). 155-63 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ishii T, et al.: "Oxidative stress-inducible proteins in macrophages"Free Radic Res. 31 (4). 351-5 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yanagawa T, et al.: "c-Abl expression in oral squamous cell carcinomas"Oral Oncol. 36 (1). 89-94 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakaso K, et al.: "Oxidative stress-related proteins A170 and heme oxygenase-1 are differently induced in the rat cerebellum under kainate-mediated excitotoxicity"Neurosci Lett. 282 (1-2). 57-60 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ishii T, et al.: "Induction of murine intestinal and hepatic peroxiredoxin MSP23 by dietary butylated hydroxyanisole"Carcinogenesis. 21 (5). 1013-16 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] YanagawaT, et al.: "Peroxiredoxin I expression in oral cancer : a potential new tumor marker"Cancer Lett. 156 (1). 27-35 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Toru Yanagawa: "c-Ab1 expression in oral squamous cell carcinomas"Oral oncology. 36(1). 89-94 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tetsuro Ishii: "Induction of murine intestinal and hepatic peroxiredoxin MSP23 by dietary butylated hydroxyanisol"Carcinogenesis. 21(5). 1013-1016 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Toru Yanagawa: "Peroxinredoxin I expression in oral cancer : a potential new tumor marker"Cancer Letters. 156. 27-35 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kazuhiro Nakaso: "oxidative stress-related proteins A170 and heme oxygenaze-1 are differentially induced in the rat cerebellum under kainate-mediated excitotoxicity"Neuroscience Letters. 282. 57-60 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kazuhiro Nakaso: "Effect of kainete-mediated excitotoxicity on the expression of rat counterparts of A170 and MSP23 stress proteins in the brain"Molecular brain research. 69. 155-163 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Toru Yanagawa: "Peroxiredoxin I expression in human thyroid tumors"Cancer Letters. 145. 127-132 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tetsuro Ishii: "Oxidative stress-inducible proteins in macrophages"Free Radical Research. 31. 351-355 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tetsuro Ishii: "Induction of murine intestinal and hepatic peroxiredoxin MSP23 by dietary butylated hydroxyanisol"Carcinogenesis. (in press).

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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