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Analyses of Molecular Mechanisms underlying Medulloblastoma Oncogenesis

Research Project

Project/Area Number 13671430
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

NAMBA Hiroki  Hamamatsu Univ. Schl. Of Med., Professor, 医学部, 教授 (60198405)

Co-Investigator(Kenkyū-buntansha) TOKUYAMA Tsutomu  Hamamatsu Univ. Schl. Of Med., Assistant Professor, 医学部附属病院, 助手 (90313957)
NISHIKAWA Shigeru  Hamamatsu Univ. Schl. Of Med., Associate Professor, 医学部, 助教授 (40135257)
YOKOTA Naoki  Hamamatsu Univ. Schl. Of Med., Assistant Professor, 医学部附属病院, 助手 (00273186)
KOIDE Masayo  Hamamatsu Univ. Schl. Of Med., Research Associate, 医学部, 助手 (40324347)
OHTA Seiji  Hamamatsu Univ. Schl. Of Med., Assistant Professor, 医学部, 助手 (80283365)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordsmedulloblastoma / developmentally regulated gene / differentially expressed gene / Subtractive suppression hybridization / Oncogenesis / Molecular Mechanisms / oncogenesis / development / subtractive cloning
Research Abstract

Although the molecular pathogenesis of medulloblastoma (MB) remains poorly understood, the importance of the Wnt and Hedgehog developmental signaling pathways has recently become apparent. In order to further the understanding of molecular events that transform a normal cerebellar cell into a MB, we utilized the technique of suppression subtractive hybridization (SSH) to identify molecules that are dysregulated and therefore may be important in MB oncogenesis. After the subtractive hybridization of cDNA from corresponding normal cerebellar tissue, SSH libraries from both human and Ptch heterozygous murine MBs were generated. Through differential screening of the libraries, over 100 cDNA fragments up-regulated in the tumor were isolated and sequenced. These sequences were identified using the NCBI BLAST program. We selected genes involved in oncogenically important processes such as cellular proliferation, apoptosis regulation, and differentiation of the cerebellum to analyze further. Genes identified in the human MB library included Unc33-like protein (ULIP), SOX4, neuronatin, the mammalian homologue of Drosophila BarH-like 1(BARHL1), the nuclear matix protein NRP/B (ENC1), and the homeobox OTX2 gene. Genes found to be up-regulated in the murine MB included cyclin D2, thymopoietin, Musashi-1, protein phosphatase 2A inhibitor-2 (I-2PP2A), and Unc5H4 (D). Using semi-quantitative RT-PCR, the mRNA expression levels for these genes are markedly higher in human MB than in the normal cerebellum. Furthermore some genes were expressed predominantly in MB. The role played by the over-expression of these genes in the transformation of normal cells remains to be fully determined.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (7 results)

All Other

All Publications (7 results)

  • [Publications] Yokota N.: "Role of Wnt pathway in medulloblastoma oncogenesis"Int. J. Cancer. 101. 198-201 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Naoki Yokota: "Role of Wnt pathway in medulloblastoma oncogenesis"Int.J.Cancer. 101. 198-201 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yokota N.: "Role of Wnt pathway in medulloblastoma oncogenesis"Int. J. Cancer. 101. 198-201 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Namba H: "Efficacy of the bystander effect in the herpes simplex virus thymidine kinase-mediated gene therapy is influenced by the expression of connexin43 in the target cells"Cancer Gene Ther. 8. 414-420 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohta S: "Cdc6 expression as a marker of proliferation activity in brain tumors"Oncol Report. 8. 1063-1066 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iuchi T: "Identification of the small interstitial deletion at chromosome 1p34-p35 and its association with poor outcome in oligodendroglial tumors"Genes Chromosomes & Cancer. 34(in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iwadate Y: "Whole-brain radiation therapy is not beneficial as an adjuvant therapy for brain metastases compared with local irradiation"Anticancer Res. 22(in press). (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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