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Study on r-and K-selection in hematological malignancies

Research Project

Project/Area Number 18591042
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionTottori University (2007)
The University of Tokyo (2006)

Principal Investigator

MOTOKURA Toru  Tottori University, Faculty of Medicine, Associate Professor (00192823)

Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,870,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2006: ¥2,700,000 (Direct Cost: ¥2,700,000)
KeywordsGene / virus / malignancy / natural selection / disease model
Research Abstract

We reported the emergence of multidrug resistant clones over-expressing P-glycoprotein under K-selection (confluent culture) using c-myc- and EJ-ras-transformed rat embryo fibroblasts (REF). Using this REF tumor model, we identified 14-3-3σ as a gene involved in the clonal evolution under K-selection. The 14-3-3σ gene is primarily expressed in epithelial cells and is frequently involved in solid tumors of epithelial origin by gene silencing via DNA methylation. In the REF tumor model, the 14-3-3σ gene was hypermethylated after γ-selection (sparse culture) and the expression was suppressed while the gene was completely demethylated after K-selection and the expression levels increased dramatically. Then we examined the expression and DNA methylation status of the 14-3-3σ gene in 41 hematological cell lines and 129 patients with hematological malignancies. The expression levels were extremely low in normal blood cells as well as in almost all hematological cell lines. However, we found the over-expression of the 14-3-3σ gene in a subset of mature lymphoid malignancies suggesting the presence of K-selection in clonal evolution in vivo.
In addition, we attempted to generate a human model of EBV-associated lymphoproliferative disorders (EBV-LPD) by using EBV-infected lymphoblastoid cell lines (LCL) and an EBV-based vector. We found cells which had been transduced with the hTERT expression plasmid proliferated and were retained in culture for a long period of time and that even monoclonal evolution with chromosomal aberration developed in vitro. Thus the comparison between human EBV-LPD and the LCL model warrants further analysis.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (10 results)

All 2007 2006

All Journal Article (8 results) (of which Peer Reviewed: 4 results) Presentation (2 results)

  • [Journal Article] Aberrant overexpression of an epithelial marker, 14-3-3σ, in a subset of hematological malignancies2007

    • Author(s)
      Motokura T, et. al.
    • Journal Title

      BMC Cancer 7

      Pages: 217-217

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Aberrant overexpression of an epithelial marker, 14-3-3a, in a subset of hematological malignancies2007

    • Author(s)
      Motokura, T., Nakamura, Y., Hiroyuki, Sato
    • Journal Title

      BMC Cancer 7

      Pages: 217-217

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Aberrant overexpression of an epithelial marker, 14-3-3σ, in a subset of hematological malignancies2007

    • Author(s)
      Toru Motokura, et. al.
    • Journal Title

      BMC Cancer 7

      Pages: 217-217

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of multidrug resistance due to multiple factors including P-glycoprotein overexpression under K-selection after MYC and HRAS oncogene activation.2006

    • Author(s)
      Nakamura Y, et. al.
    • Journal Title

      Int. J. Cancer 118

      Pages: 2448-2454

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Differential 14-3-3σ DNA methylation and expression in c-myc-and activated H-ras-transformed cells under r- and K-selection.2006

    • Author(s)
      Sato H, et. al.
    • Journal Title

      Cancer Lett. 236

      Pages: 105-114

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Development of multidrug resistance due to multiple factors includingP-glycoprotein overexpression under K-selection after MYCand HRASoncogene activation2006

    • Author(s)
      Nakamura, Y., Sato, H., Motokura, T
    • Journal Title

      Int. J. Cancer 118(10)

      Pages: 2448-2454

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Differential 14-3-3a DNA methylation and expression in c-myc and activated H-ras-transformed cells under r and K-selection2006

    • Author(s)
      Sato, H., Nakamura, Y., Motokura, T
    • Journal Title

      Cancer Lett 236

      Pages: 105-114

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] 造血器腫瘍における14-3-3σ遺伝子の発現解析2006

    • Author(s)
      本倉 徹 他
    • Journal Title

      臨床血液 47・9

      Pages: 264-264

    • Related Report
      2006 Annual Research Report
  • [Presentation] 造血器腫瘍における14-3-3σ遺伝子の発現解析2006

    • Author(s)
      本倉 徹、佐藤博之
    • Organizer
      第68回日本血液学会・第48回日本臨床血液学会合同総会
    • Place of Presentation
      福岡
    • Year and Date
      2006-10-06
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Analysis of 14-3-3a expression in hematological malignancies2006

    • Author(s)
      Motokura, T., Sato, H
    • Organizer
      The United General Meeting of the Japanese Society of Hematology and the Japanese Scoiety of Clinical Hematology
    • Place of Presentation
      Fukuoka
    • Year and Date
      2006-10-06
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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