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Investigation of Functional Roles of New p53 Family Members - p73, p51, and p40 in Brain Tumors

Research Project

Project/Area Number 11470282
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

TADA Mitsuhiro  Hokkaido Univ., Inst. for Genet. Med., Asso. Prof., 遺伝子病制御研究所, 助教授 (10241316)

Co-Investigator(Kenkyū-buntansha) MORIUCHI Tetsuya  Hokkaido Univ., Inst. for Genet. Med., Prof., 遺伝子病制御研究所, 教授 (20174394)
ISHII Nobuaki  Hokkaido Univ., Grad. School of Med., Inst., 大学院・医学研究科, 助手 (70312353)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2001: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2000: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 1999: ¥5,100,000 (Direct Cost: ¥5,100,000)
Keywordsp53 family / p73 / p51 / p63 / p40 / brain tumor
Research Abstract

In this research project, we investigated functional roles of new p53 family members - p73, p51, and p40 in human brain tumors. We developed new yeast-based assays to measure transcriptional activity of p73 and p63 and applied to brain tumors. As the results, we obtained the followings:
1) We applied a newly developed yeast p73 functional assay to a total of 52 cases of glioblastoma and meningioma, and found no p73 mutation in these tumors. We showed, however, that expression of α, β, γ, and ε isoforms of p73 correlates with malignancy of meningioma (Brain Pathol., 2001).
2) Recessive p53 mutants are known to specifically inhibit p73. We showed an allele specific selection of Arg72, which strongly inhibits p73, by recessive p53 mutation, but not by dominant negative p53 mutations (Carcinogenesis, 2001).
3) We reported transcriptional activity of p73 mutants - P405R and P425L found in human tumors (Oncogene, 2001).
4) We developed a quantitative transcriptional assay for p53, p73, and p63 tumor suppressors, and will publish the results as soon.

Report

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

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Tada M: "Inactivate the remaining p53 allele or the alternate p73? Preferential selection of the Arg72 polymorphism in cancers with recessive p53 mutants but not transdominant mutants"Carcinogenesis. 22. 515-517 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nozaki M: "p73 is not mutated in meningiomas as determined with a functional yeast assay but p73 expression increases with tumor grade"Brain Pathol. 11. 296-305 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Naka M: "Functional characterization of naturally occurring mutants (P405R and P425L) of p73alpha and p73beta found in neuroblastoma and lung cancer"Oncogene. 20. 3568-3572 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ikeda J: "Restoration of endogenous wild type p53 activity in a glioblastoma cell line with intrinsic temperature-sensitive p53 induces growth arrest but not apoptosis"Int J Cancer. 94. 35-43 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nozaki M: "Roles of the functional loss of p53 and other genes in astrocytoma tumorigenesis and progression"Neuro-oncology. 1. 149-162 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ozaki T: "Deletion of the COOH-terminal region ofp73alpha enhances both its transactivation function and DNA-binding activity but inhibits induction of apoptosis in mammalian cells"Cancer Res. 59. 5902-5907 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 多田光宏: "脳神経外科医に必要な分子生物学"三輪書店, 東京(分担). 86-99 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tada M.: "Inactivate the remaining p53 allele or the alternate p73? - Preferential selection of the Arg72 polymorphism in cancers with recessive p53 mutants but not transdominant mutants"Carcinogenesis. 22. 515-517 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nozaki M.: "p73 is not mutated in meningiomas as determined with a functional yeast assay but p73 expression increases with tumor grade"Brain Pathol.. 11. 296-305 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Naka M.: "Functional characterization of naturally occurring mutants (P405R and P425L) of p73alpha and p73beta found in neuroblastoma and lung cancer"Oncogene. 20. 3568-3572 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ikeda J.: "Restoration of endogenous wild type p53 activity in a glioblastoma cell line with intrinsic temperature-sensitive p53 induces growth arrest but not apoptosis"Int. J. Cancer. 94. 35-43 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nozaki M.: "Roles of the functional loss of p53 and other genes in astrocytoma tumorigenesis and progression"Neuro-oncology. 1. 149-162 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ozaki T.: "Deletion of the COOH-terminal region of p73alpha enhances both its transactivation function and DNA-binding activity but inhibits induction of apoptosis in mammalian cells"Cancer Res.. 59. 5902-5907 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tada M.: "Molecular Biology for Neurological Surgeons"Mitsuwa-Shoten, Tokyo. 86-89 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tada M.: "Inactivate the remaining p53 allele or the alternate p73? -Preferential selection of the Arg72 polymorphism in cancers with recessive p53 mutants but not transdominant mutants"Carcinogenesis. 22. 515-517 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nozaki M.: "p73 is not mutated in meningiomas as determined with a functional yeast assay but p73 expression increases with tumor grade"Brain Pathol. 11. 296-305 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Naka M.: "Functional characterization of naturally occurring mutants (P405R and P425L) of p73alpha and p73beta found in neuroblastoma and lung cancer"Oncogene. 20. 3568-3572 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsuiki H.: "Mechanism of hyperploid cell formation induced by microtubule inhibiting drug in glioma cell lines"Oncogene. 20. 420-4353 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ikeda J.: "Restoration of endogenous wild type p53 activity in a glioblastoma cell line with intrinsic temperature-sensitive p53 induces growth arrest but not apoptosis"Int J Cancer. 94. 35-43 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ishii N.: "Alternative EWS-FLI1 fusion gene and MIC2 expression in peripheral and central primitive neuroectodermal tumors"Neuropathology. 21. 40-44 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 多田光宏: "脳神経外科医に必要な分子生物学"三輪書店,東京(分担). 86-99 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nozaki M, Tada M, et al.: "No p73 mutations in meningiomas as determined with a simple functional yeast assay, instead, increased p73 expression characterizes malignant meningiomas."Brain Pathology. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tada M, Furuuchi K, et al.: "Inactivate the Remaining p53 Allele or the Alternate p73? -Preferential selection of the Arg72 polymorphism in cancers with recessive p53 mutants but not transdominant mutants."Carcinogenesis. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Asaoka K, Tada M, et al.: "Efficient adenoviral gene delivery in malignant glioma cells depends on the expression levels of coxsackievirus and adenovirus receptor."Journal of Neurosurgery. 92. 1002-1008 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Zhang C-L, Tada M, et al.: "Detection of PTEN nonsense mutation and psiPTEN expression in central nervous system high-grade astrocytic tumors by a yeast-based stop codon assay."Oncogene. 19. 4346-4353 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nozaki M., Tada M., et al.: "Development of a yeast functional assay for the putative tumor suppressor gene p73 to assess function and detect mutations in clinical samples"Neuro-Oncology. 1. S81 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ozaki, T., Tada M., et al.: "Deletion of the C-terminal region of p73α enhances both its transactivation function and DNA-binding activity but inhibits induction of apoptosis in mammalian cells"Cancer Research. 59. 5902-5907 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nozaki M., Tada M., et al.: "Roles of the functional loss of p53 and other genes in astrocytoma tumorigenesis and progression"Neuro-Oncology. 1. 149-162 (1999)

    • Related Report
      1999 Annual Research Report

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

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