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1998 Fiscal Year Final Research Report Summary

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
Keywordsp53 / brain tumor / knockout mice / glioblastoma / medulloblastoma / apoptosis / エチルニトロソウレア / DNA損傷
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.

  • Research Products

    (10 results)

All Other

All Publications (10 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 1999-12-08  

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