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Elucidation in the mechanism of human renal cell carcinoma cancer growth and micrometastasis with inactivation of VHL

Research Project

Project/Area Number 14370515
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionKochi University School of Medicine

Principal Investigator

SHUIN Taro  Kochi University, school of medicine, Professor, 医学部, 教授 (80179019)

Co-Investigator(Kenkyū-buntansha) INOUE Keiji  Kochi University, school of medicine, Assistant Professor, 医学部附属病院, 講師 (00294827)
OKUDA Heiwa  Kochi University, school of medicine, Research Associate, 医学部, 助手 (60325420)
KAMADA Masayuki  Kochi University, school of medicine, Research Associate, 医学部附属病院, 助手 (90304683)
ASO Teijiro  Kochi Universith, school of medicine, Professor, 医学部, 教授 (20291289)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥11,400,000 (Direct Cost: ¥11,400,000)
Fiscal Year 2003: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥7,800,000 (Direct Cost: ¥7,800,000)
Keywordstumor suppressor gene / methylation / renal cell carcinoma / VHL gene / VEGF / MIRC9 / Hypoxia Inducible Factor / メチル化 / CpG island methylator phenotype / VHL / Ubiquitin liagase
Research Abstract

Since human renal cell carcinoma (RCC) is resistant against chemotherapy or radiation therapy, there is no definitive curable treatment for the advanced RCC or its distant metastasis. Several cytokines shows only minor effect. Human clear cell RCCs compose of 80% of whole human RCCs. It is well known that von Hippel-Lindau (VHL) disease gene is mutated and inactivated in 70% of human clear cell RCCs. VHL protein makes complex with ElonginB & C to VBC complex in normal cells and works as ubiquitin ligase. It ubiquitates hypoxia inducible factor (HIF) at normoxic condition. HIF is degradeted at proteasome. When VHL gene is inactivated, HIF is upregulated at normoxic condition. This condition result in the high level of HIF, thereby overproduction of VEGF or Glucose transporter. That causes in a good condition for human RCCs. However, this condition itself is not sufficient for the explanation of the tumor development for human RCCs. We tried to detect methylated and inactivated possible tumor suppressor genes in human RCCs, which explains tumor development and growth together with inactivation of VHL. Several genes such as RASSF1A, CHFA, CACNA1G, TMS1,Cox2,DAPK, MINT, MINT2,MIRC9,MIRC37 are methylated and inactivated in human clear cell RCCs in Japan at different kind of extent. Similar findings are obtained in human clear cell lines. Therefore it is regarded that inactivation of the VHL gene with these genes are responsible for the development of human RCCs. Several pathways such as, HIF, VEGF, and Elongin are involved for the development and progression of human clear cell RCCs.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (12 results)

All 2005 2004 2003

All Journal Article (12 results)

  • [Journal Article] Hypoxia-Inducible Factor-Ialpha Is Involved in the attenuation of Experimentally Induced Rat Glomerulonephritis.2005

    • Author(s)
      kudo Y
    • Journal Title

      Nephron Exp Nephrol. 100・(2)

      Pages: 95-103

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Levels of angiogenesis and Expression of angiogenesis-related genes are prognostic for organ-specific metastasis of renal cell carcinoma.2005

    • Author(s)
      Fukata S
    • Journal Title

      Cancer 103・(5)

      Pages: 931-942

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Hypoxia-Inducible Factor-1alpha Is Involved in the Attenuation of Experimentally Induced Rat Glomerulonephritis.2005

    • Author(s)
      KudoY, Kakinuma Y, Mori Y, Morimoto N, Karashima T, Furihata M, Sato T, Shuin T, Sugiura T.
    • Journal Title

      Nephron Exp Nephrol. 100(2)

      Pages: 95-103

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Levels of angiogenesis and expression of angiogenesis-related genes are prognostic for organ-specific metastasis of renal cell carcinoma.2005

    • Author(s)
      Fukata S, Inoue K, Kamada M, Kawada C, Furihata M, Ohtsuki Y, Shuin T.
    • Journal Title

      Cancer. 103(5)

      Pages: 931-942

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Hypermethylation of the RASSFIA tumor suppressor in Japanese clear cell renal cell carcinoma.2004

    • Author(s)
      Tokinaga K
    • Journal Title

      Oncol Rep 12・(4)

      Pages: 805-810

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Recent advances in ideas on the molecular Pathology and clinical aspects of Von hippel-Lindau disease.2004

    • Author(s)
      Shuin T
    • Journal Title

      Int J Clin Oncol 9・(4)

      Pages: 283-287

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Hypermethylation of the RASSF1A tumor suppressor gene in Japanese clear cell renal cell carcinoma.2004

    • Author(s)
      Tokinaga K, Okuda H, Nomura A, Ashida S, Furihata M, Shuin T.
    • Journal Title

      Oncol Rep. 12(4)

      Pages: 805-810

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Recent advances in ideas on the molecular pathology and clinical aspects of Von Hippel-Lindau disease.2004

    • Author(s)
      Shuin T, Yamazaki I, Tamura K, Kamada M, Ashida S.
    • Journal Title

      Int J Clin Oncol. 9(4)

      Pages: 283-287

    • NAID

      10013569590

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Identification of Eloa-BPI,anovel Elongin A binding protein with an exonuclease homology domain.2003

    • Author(s)
      Tamura K
    • Journal Title

      Biochem Biophys Res commun 309・(1)

      Pages: 189-195

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Molecular detection of von Hippel-Lindau gene mutations in urine and lymph node samples in patients with renal cell carcinoma : potential biomarkers for early diagnosis and postoperative metastatic status.2003

    • Author(s)
      ashida S
    • Journal Title

      J Urol 169

      Pages: 2089-2093

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Identification of EloA-BPl, a novel Elongin A binding protein with an exonuclease homology domain.2003

    • Author(s)
      Tamura K, MIyata K, Sugahara K, Onishi S, Shuin T, Aso T,.
    • Journal Title

      Biochem Biophys Res Commun. 309(1)

      Pages: 189-195

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Molecular detection of von Hippel-Lindau gene mutations in urine and lymph node samples in patients with renal cell carcinoma : potential biomakers for early diagnosis and postoperative metastatic status.2003

    • Author(s)
      Ashida S, Furihara M, Tanimura M, Sugita O, Yamashita M, Miura T, Moriyama M, Shuin T.
    • Journal Title

      J Urol. 169(6)

      Pages: 2089-2093

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary

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Published: 2002-04-01   Modified: 2016-04-21  

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