1998 Fiscal Year Final Research Report Summary
Analysis of the brain tumor transplacentally induced in p53 knockout mice
| Project/Area Number |
09470061
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | The University of Tokyo |
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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)
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| 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)
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| Project Period (FY) |
1997 – 1998
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| Keywords | p53 / brain tumor / knockout mice / glioblastoma / medulloblastoma / apoptosis / エチルニトロソウレア / DNA損傷 |
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| 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.
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
