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Analysis of the brain tumor transplacentally induced in p53 knockout mice

Research Project

Project/Area Number 09470061
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionThe University of Tokyo

Principal Investigator

ISHIKAWA Takatoshi  The University of Tokyo, Graduate School of Medicine, Department of Molecular Pathology Professor, 大学院・医学系研究科, 教授 (30085633)

Co-Investigator(Kenkyū-buntansha) ODA Hideaki  The University of Tokyo, Graduate School of Medicine, Department of Molecular Pa, 大学院・医学系研究科, 助教授 (40214142)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥9,400,000 (Direct Cost: ¥9,400,000)
Fiscal Year 1998: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 1997: ¥5,200,000 (Direct Cost: ¥5,200,000)
Keywordsp53 / brain tumor / knockout mice / glioblastoma / medulloblastoma / apoptosis / エチルニトロソウレア / DNA損傷 / neu遺伝子、活性化
Research Abstract

The glioma is the most common tumor of the central nervous system in man, however, it has rarely been induced in mice. Recently, we observed in p53 knockout mice a high incidence (70%) of glial tumors (glioblastomas) after prenatal (12.5 of gestational day) ethylnitrosourea(ENU)exposure and suggest that loss of p53 function is early and important event in tumorigenesis. This led to the question of how p53 loss influence brain tumorigenesis in mice. We disclosed that carcinogen-induced apoptotic cell death is a p53-dependent pathway in specific regions of embryonal brain which also overlap with origin of glial tumors. At the gestational day of 12.5, in addition, glia shows most proliferative activity. Therefore, we considered that DNA damage induced by carcinogen exposure, inhibition of apoptosis and proliferative activity play important roles in brain tumorigenesis in mice. According to our hypothesis, we injected ENU in neonatal mice (1 day after birth). In this experiment, we observed p53-dependent and carcinogen-induced apoptosis in external granular layer of cerebellum, and 2 month later, medulloblastomas (60%) developed in the cerebellum.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Oda, Ishikawa, T.et al.: "Loss of p53 is an early event induction of brain tumors in mice by transplacental carcinogen exposure." Cancer Res.57. 646-650 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y, Imai.,T,Ishikawa.et al.: "p16INK4 Gene mutations are relatively frequent in ampullary carcionomas." Jpn.J.Cancer Res. 88. 941-946 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H, Oda.,T, Ishikawa.et al.: "Loss of Imprinting of IGF2 in Renal-Cell Carcinomas." Int.J.Cancer. 75. 343-346 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H, Kawate.,M, Sekiguchi.et al.: "Separation of killing and tumorigenic effects of an alkylating agent in mice defective in two of the DNA repair genes." Proc.Natl.Acad.Sci.USA. 595. 5116-5120 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Honda.,H.Hirai.et al.: "Cardiovascular anomaly,impaired actin bundling and resistance to Src-induced transformation on mice lacking p130Cas." Nature Genetics. 19. 361-365 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Oda, H., Zhang, S., Tsurutani, N., Shimizu, S., Nakatsuru, Y., Aizawa, S.and Ishikawa, T: "Loss of p53 is an early event induction of brain tumors in mice by transplacental carcinogen exposure." Cancer Res.57. 646-650 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y,Imai., N,Tsurutani., H,Oda., Y,Nakatsuru., T,Inoue.and T,Ishikawa.: "p16INK4 Gene mutations are relatively frequent in ampullary carcionomas." Jpn.J.Cancer Res.88. 941-946 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H,Oda., H,Kume., Y,Shimizu., T,Inoue.and T,Ishikawa.: "Loss of Imprinting of IGF2 in Renal-Cell Carcinomas." Int.J.Cancer. 75. 343-346 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H,Kawate., K,Sakumi., T,Tsuzuki., Y,Nakatsuru., T,Ishikawa., S,Takahishi., H,Takano., T,Noda.and M,Sekiguchi.: "Separation of killing and tumorigenic effects of an alkylating agent in mice defective in two of the DNA repair genes." Proc.Natl.Acad.Sci.USA. 95. 5116-5120 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Honda., H.Oda., T.Nakamoto., Z.Honda., R.Sakai., T.Suzuki., T.Saito., K.Nakamura., K.Nakao., T.Ishikawa., M.Katsuki., Y.Yazaki and H.Hirai.: "Cardiovascular anomaly, impaired actin bundling and resistance to Src-induced transformation on mice lacking p130Cas." Nature Genetics. 19. 360-365 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Oda,H Ishikawa,T.et al.: "Loss of p53 is an early event induction of brain tumors in mice by transplacental carcinogen exposure." Cancer Res.57. 646-650 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y,Imai.,T,Ishikawa.et al.: "p16^<INK4> Gene mutations are relatively frequent in ampullary carcionomas." Jpn.J.Cancer Res. 88. 941-946 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] H,Oda.,T,Ishikawa.et al.: "Loss of Imprinting of IGF2 in Renal-Cell Carcinomas." Int.J.Cancer. 75. 343-346 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H,Kawate.,M,Sekiguchi.et al.: "Separation of killing and tumorigenic effects of an alkylating agent in mice defective in two of the DNA repair genes." Proc.Natl.Acad.Sci.USA. 95. 5116-5120 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Honda.,H.Hirai.et al.: "Cardiovascular anomaly,impaired actin bundling and resistance to Src-induced transformation on mice lacking p130^<Cas>." Nature Genetics. 19. 361-365 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Oda,H., Ishikawa T.et al.: "Loss of p53 is an early event induction of brain tumors in mice by tranceplacental carcionogen exposure." Cancer Res. 57. 646-650 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Arai,M., Ishikawa,T.et al.: "Mutations of the Ki-ras,p53 and APC genes in adenocarcinomas of the human small intestine." Int,J.Cancer. 70. 390-395 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Suwiwat,S., Ishikawa,T.et al.: "Prevalence of p53 mutations and protein expression in esophageal cancers in southern Thailand." Int.J.Cancer. 72. 23-26 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Iwakuma,T., Ishikawa,T.et al.: "High incidence of nitrosamine-induced tumorigenesis in mice lacking DNA repair methyltransferase." Carciogenesis. 18. 1631-1635 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Imai,Y., Ishikawa,T.et al.: "Frequent somatic mutations of the APC and p53 genes in sporadic ampullary carcinomas." Jpn.J.Cancer Res.88. 941-946 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Imai,Y., Ishikawa,T.et al.: "p16^<INK4> gene mutations are relatively frequent in ampullary carcionamas." Jpn.J.Cancer Res.88. 941-946 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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