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Molecular clock mechanism of cancer

Research Project

Project/Area Number 16390042
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical pharmacy
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

OHDO Shigehiro  KYUSHU UNIVERSITY, Faculty of Pharmaceutical Sciences, Prof., 大学院・薬学研究院, 教授 (00223884)

Co-Investigator(Kenkyū-buntansha) TO Hideto  KYUSHU UNIVERSITY, Faculty of Pharmaceutical Sciences, Assistant Prof., 大学院・薬学研究院, 助手 (90346809)
HIGUCHI Shun  KYUSHU UNIVERSITY, Faculty of Pharmaceutical Sciences, Prof., 大学院・薬学研究院, 教授 (40218699)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2005: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥11,300,000 (Direct Cost: ¥11,300,000)
KeywordsBiological rhythm / Biological clock / Cancer
Research Abstract

Although the alteration of circadian rhythm is suggested to increase the risk of cancer, the relationship between the circadian clock and tumorigenesis has not been clarified. Firstly, we constructed the liver tumor induced by Diethylnitrosamine (DEN) in rats. Hepatocellular carcinoma (HCC) were found in rats administered with DEN (80 mg/l or 160 mg/l), but there was no HCC in rats administered with DEN (40 mg/l). Body weight decreased strongly from the early stage of DEN (160 mg/l) and showed the case of death. From these results, we decided concentration of DEN at 80 mg/l to induce tumor in rat liver. Secondly, we investigated the influence of DEN on the 24-hr rhythm of clock genes mRNA and proteins in rats liver. In the control group, the mRNA levels of Clock, Bmal1,Per1,Per2 and Cry1 in the liver showed a significant 24-hr trhythm (P<0.05,respectively). In DEN treated group, the mRNA levels of Clock, Bmal1,Per2 and Cry1 mRNA expression in the liver showed a significant 24-hr rhythm … More (P<0.05,respectively). But, the mRNA level of Per1 showed no 24-hr rhythm. Moreover, the mRNA levels of Clock,Per1,Per2 and Cry1 in the liver was lower in DEN treated group than control group. DEN caused a low amplitude and/or a phase shift of each rhythm. Bmal1 mRNA expression in the liver showed the same amplitude as control group. In control group, CLOCK protein expression in the liver showed no rhythmic expression. CLOCK protein expression was lower in DEN treated group than control group. In control group, PER2 protein expression in the liver showed 24-hr rhythm. PER2 protein expression was lower in DEN treated group than control group. In the present study, the chronic administration of DEN induced liver tumor in rats, and altered the 24-hr rhythm of clock genes and their protein levels. Also, circadian disruption by surgical ablation of the SCN is reported to accelerate tumor progression. Therefore, the alteration of the 24-hr rhythm of clock gene is considered to be important in the process of tumorigenesis. Less

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (10 results)

All 2005 2004

All Journal Article (10 results)

  • [Journal Article] Effect of haloperidol on mPerl gene expression in mouse SCN.2005

    • Author(s)
      Viyoch, J et al.
    • Journal Title

      Journal of Biological Chemistry 280,8

      Pages: 6309-6315

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cell-cycle-dependent pharmacology of methotrexate in HL-602005

    • Author(s)
      Yamauchi, A. et al.
    • Journal Title

      Journal of Pharmacological Sciences 99

      Pages: 335-341

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effect of haloperidol on mPer1 gene expression in mouse SCN.2005

    • Author(s)
      Viyoch, J et al.
    • Journal Title

      Journal of Biological Chemistry 280(8)

      Pages: 6309-6315

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cell-cycle-dependent pharmacology of methotrexate in HL-602005

    • Author(s)
      Yamauchi, A. et al.
    • Journal Title

      J Pharmacol Sci 99

      Pages: 335-341

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Effect of haloperidol on mPer1 gene expression in mouse SCN.2005

    • Author(s)
      Viyoch, J et al.
    • Journal Title

      Journal of Biological Chemistry 280,8

      Pages: 6309-6315

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 24-hr oscillation of mouse methionine aminopeptidase2, a regulator of tumor progression, is regulated by clock gene proteins.2004

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

      Cancer Research 64

      Pages: 8328-8333

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Influence of feeding schedule on 24-h rhythm of hepatotoxicity induced by acetaminophen in mice2004

    • Author(s)
      Matsunaga, N. et al.
    • Journal Title

      Journal of Pharmacology & Experimental Therapeutics 311,2

      Pages: 594-600

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 24-hr oscillation of mouse methionine aminopeptidase2,a regulator of tumor progression, is regulated by clock gene proteins.2004

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

      Cancer Research 64

      Pages: 8328-8333

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Influence of feeding schedule on 24-h rhythm of hepatotoxicity induced by acetaminophen in mice2004

    • Author(s)
      Matsunaga, N. et al.
    • Journal Title

      Journal of Pharmacology & Experimental Therapeutics 311(2)

      Pages: 594-600

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 24-hr oscillation of mouse methionine aminopeptidase2, a regulator of tumor progressions is regulated by clock gene proteins.2004

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

      Cancer Research 64

      Pages: 8328-8333

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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