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Cloning of immortalization genes of rat type 1 astroglia

Research Project

Project/Area Number 05807125
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Cerebral neurosurgery
Research InstitutionOsaka University

Principal Investigator

HIRAGA Shoju  Osaka University, Neurosurgery, Assistant, 医学部, 助手 (40243232)

Co-Investigator(Kenkyū-buntansha) SAKOTA Saburo  Osaka University, Neurology, Assistant, 医学部, 助手 (00178625)
TAKI Takuyu  Osaka University, Neurosurgery, Hospital Staff, 医学部・付属病院, 医員
HAYAKAWA Toru  Osaka University, Neurosurgery, Professor, 医学部, 教授 (20135700)
有田 憲生  近畿大学, 医学部, 助教授 (80159508)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1994: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1993: ¥900,000 (Direct Cost: ¥900,000)
KeywordsImmortalization / Astroglia / Glioma / p53 / Ethylnitrosourea / 悪性グリオーマ
Research Abstract

Although malignant changes from low-grade gliomas to high-grade ones have bee elucidated recently, early neoplastic changes of normal astroglia are not well understood. We reported that Cultured type 1 astroglia could be transformed in a short term by a Singe high dose of ENU and that alterations, probably missense mutations, of tumor suppressor p53 gene closely related to the cell transformation. Moreover, we established 5 immortalized type 1 astroglial cell lines. All these cell lines maintained, polygonal shape of the cell, low saturation density, regular pavement growth, slow growth, and did not have tumorigenicity in athymic mice. However, these cells showed high motility to glioma motility factor, expressed tenascin and these characteristics differed from normal astroglia.
The tumor suppressor p53 gene was extensively examined in these cell lines by various molecular biological methods. While missense mutations were demonstrated in all ENU transformed cell lines, no p53 alterations were observed in these immortalized cell lines. Thus, immortalization of the type 1 astroglia was regulated by other gene (s) than p53 or an escape from other mechanism to control cell growth and senescence. We attempted differential hybridization between normal and immortalized type 1 astroglias cDNAs. By colony screening, we obtained 200 candidate genes for immortalization and we now under investigation of these genes. Thus, this work elucidated the role of p53 in astroglial oncogenesis and further investigation on glial immortalization will provide the early genetic alteration of astroglial carcinogenesis and may lead to a new strategy for glioma therapy.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Hiraga S,et al: "Transformation of type 1astrocytes with N-ethyl-N-nitrosourea:Establishment of an in vitro system and the role of the p53 gene" GLIA. 13. 51-63 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 平賀 章壽 他: "培養ラット胎児アストログリア細胞のENU発癌-N-ethyl-N-nitrosourea(ENU)誘発変異細胞出現とその生物学的検討-" 脳と神経. 45. 343-347 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hiraga S,et al: "N-ethyl-N-nitrosourea(ENU)induced malignant transformation of rat type-1 astrocytes in vitro and the alterations of p53 tumor suppressor gene" J Neuro-Oncol. 15. S11- (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hayakawa T,et al: "Primary central nervous system lymphoma in Japan.-A retrospective cooperative study by CNS-lymphoma study group in Japan" J Neuro-Oncol. 19. 197-215 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Higuchi M,et al: "Expression of tenascin in human gliomas:its relation to histological malignancy,tumor differentiation and angiogenesis" Acta Neuropathol. 85. 481-487 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Taki T,et al: "Anti-proliferative effects of TNP-470 on human malignant glioma in vivo:potent inhibition of tumor angiogenesis." J Neuro-Oncol. 19. 251-258 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hiraga S,Arita N,Ohnishi T,Izumoto S,Taki T,Yamamoto H,Higuchi M,Hayakawa T: "Transformation of type 1 astrocytes with N-ethy1-N-nitrosourea : Establishment of an in vitro system and the role of the p53 gene" GLIA. 13. 51-63 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hayakawa T,Takakura K,Abe H,Yoshimoto T,Tanaka R,Sugita K,Kikuchi H,Uozumi T,Hori M,Fukui H,Ushio Y,Nomura K,Matsutani M,Mohri N,Kumanishi T,Aozasa K,Nagashima K: "Primary central nervous system lymphoma in Japan.-A retrospective, cooperative study by CNS-lymphoma study group in Japan" J Neuro-Oncol. 19. 197-215 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ohnishi T,Arita N,Hayakawa T,Kawahara K,Kato K,Kakinuma A: "Purification of motility factor (GMF) from human malignant glioma cells and its biological significance in tumor invasion." Biochem Biophys Res Comm. 193. 518-525 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Higuchi M,Ohnishi T,Arita N,Hiraga S,and Hayakawa T: "Expression of tenascin in human gliomas : its relation to histological malignancy, tumor differentiation and angiogenesis" Acta Neuropathol. 85. 481-487 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Taki T,Ohnishi T,Arita N,Hiraga S,Youichi S,Izumoto S,Mori K,Hayakawa T: "Anti-proliferative effects of TNP-470 on human malignant glioma in vivo : potent inhibition of tumor angiogenesis" J Neuro-Oncol. 19. 251-258 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Higuchi M,Ohnishi T,Arita N,Hiraga S,Hayakawa T: "Leptomeningeal dissemina-tion of malignant glioma : immunohistochemical analysis of tenascin and glial fibrillary acidic protein" Clin Neuropathol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yamasaki M,Arita N,Hiraga S,Izumoto S,Morimoto K,Nakatani S,Fujitani Ken, Sato N,T Hayakawa: "X-linked hydrocephalus in Japan-Clinical and neuroradiological study-" J Neurosurgery. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hiraga S,Arita N,Ohnishi T,Taki T,Yamamoto H,Higuchi M,Hayakawa T: "N-ethyl-N-nitrosourea(ENU) induced malignant transformation of rat type-1 astrocytes in vitro and the alterations of p53 tumor suppressor gene." J Neuro-Oncol. 15. S11 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Arita N,Ohnishi T,Hiraga S,Yamamoto H,Taki T,Izumoto S,Higuchi M,Hayakawa T,Kusakabe M,Sakakura T: "Tenascin expression in human glioma cell lines and tissue." J Neuro-Oncol. 15. S2 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] T.Ohnishi, Arita N,Hiraga S,Hayakawa T: "Role of Glioma derived motility factor (GMF) in tumor invasion" J Neuro-Oncol. 15. S19 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hiraga S,et al: "Transformation of type 1 astrocytes with N-ethyl-N-nitrosourea:Establishment of an in vitro system and the role of the p53 gene" GLIA. 13. 51-63 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 平賀章壽他: "培養ラット胎児アストログリア細胞のENU発癌-N-ethyl-N-nitrosourea(ENU)誘発変異細胞出現とその生物学的検討-" 脳と神経. 45. 343-347 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hiraga S,et al: "N-ethyl-N-nitrosourea(ENU)induced malignant transformation of rat type-1 astrocytes in vitro and the alterations of p53 tumor suppressor gene." J Neuro-Oncol. 15. S11- (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hayakawa T,et al: "Primary central nervous system lymphoma in Japan.-A retrospective cooperative study by CNS-lymphoma study group in Japan" J Neuro-Oncol. 19. 197-215 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Higuchi M,et al: "Expression of tenascin in human gliomas: its relation to histological malignancy,tumor differentiation and angiogenesis" Acta Neuropathol. 85. 481-487 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Taki T,et al: "Anti-proliferative effects of TNP-470 on human malignant glioma in vivo:potent inhibition of tumor angiogenesis." J Neuro-Oncol. 19. 251-258 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 平賀 章壽: "悪性グリオーマに対するモルフォリノアンスラサイクリン系抗癌剤MX2の効果-ACNUおよびetoposideとの交叉耐性の有無に関する検討" KARKINOS. 5. 1328-1333 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] T.Ohnishi: "Role of Glioma derived motility factor(GMF)in tumor invasion." J Neuro-Oncol. 15. S19 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] T.Hayakawa: "Primary central nervous system lymphoma in Japan-A retrosrective cooperative study by CNS-Lymphoma Study Group in Japan-" J Neuro-Oncol. (in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] T.Taki: "Anti-proliferative effects of TNP-470 on human malignant glioma in vivo:potent inhibition of tumor angiogenesis." J Neuro-Oncol. (in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] M.Higuchi: "Expression of tanascin in human gliomas:its relation to histological malignancy,tumor dedifferentiation and angiogenesis." Acta Neuropathol(Berl). 85. 481-487 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] N.Arita: "Tenascin expression in human glioma cell lines and tissue." J Neuro-Oncol. 15. S2 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 平賀 章壽: "Annual Review 神経" 中外医学社, 178-187 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] S.Hiraga: "Biological aspects of brain tumors" Springer-Verlag, 273-280 (1991)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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