• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Effect of protein C inhibitor on renal cell carcinogenesis and on tumor invasion, growth and metastasis

Research Project

Project/Area Number 16591592
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionMie University

Principal Investigator

HAYASHI Tatsuya  Mie University, Graduate School of Medicine, Lecturer, 大学院・医学系研究科, 講師 (00242959)

Co-Investigator(Kenkyū-buntansha) SUZUKI Koji  Mie University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (70077808)
OKAMOTO Takayuki  Mie University, Graduate School of Medicine, Assistant Professor, 大学院・医学系研究科, 助手 (30378286)
鎌田 春彦  国立医薬食品衛生研究所, 基盤研究第二プロジェクト, 主任研究官 (00324509)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsProtein C inhibitor / renal cell carcinoma / CpG methylation / breast cancer cell / serine protease inhibitor / invasion / metastasis / reactive site / DNAメチル化 / 腎近位尿細管上皮細胞
Research Abstract

Protein C inhibitor (PCI), a member of the serine protease inhibitor (serpin) family, regulates the anticoagulant protein C pathway and inhibits urinary plasminogen activator (uPA), a mediator of tumor cell invasion. We recently demonstrated that PCI expression is significantly decreased in renal carcinoma cells derived from renal proximal tubular epithelial cells, and that PCI suppresses in vitro Matrigel invasion of renal carcinoma cells by inhibiting uPA. Furthermore, we also suggested that decreased expression of PCI in renal cell carcinoma (RCC) is mainly caused by methylation of the promoter region of PCI gene. In the present study, we elucidated the detailed mechanism of decreased expression of PCI induced by PCI gene methylation in RCC, and evaluated the effect of human PCI and its inactive derivatives on tumor cell invasion in vitro, and on tumor growth and metastasis in vivo using human breast cancer (MDA-231) cells. Hydrogen bisulfite DNA sequence showed that four out of thi … More rteen CpG sequence located near transcription initiation site are specifically methylated in PCI gene of RCC. Luciferase reporter gene assay using methylated PCI gene fragment showed that transcriptional activity of PCI gene promoter fragment is decreased by methylation of these four CpG sequence near transcription initiation site. On the other hand, the in vitro invasiveness of MDA-231 cells expressing intact PCI (MDA-PCI) was significantly decreased as compared to MDA-231 cells expressing inactive R354APCI (MDA-R354APCI) or the N-terminal fragment of PCI (MDA-NTPCI). Further, in vivo growth and metastatic potential of MDA-PCI, MDA-R354APCI and MDA-NTPCI cells in severe combined immunodeficient (SCID) mice were significantly decreased as compared to MDA-Mock cells. Overall, these studies showed that, decreased PCI expression in RCC is mainly caused by specific CpG methlation of PCI gene promoter, and in addition to its reactive site-dependent action, PCI also regulates tumor growth and metastasis independently of its protease inhibitory activity. Less

Report

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

    (17 results)

All 2006 2004

All Journal Article (17 results)

  • [Journal Article] ヒトプロテインCインヒビター遺伝子トランスジェニックマウス.2006

    • Author(s)
      林 辰弥
    • Journal Title

      血栓と循環 13

      Pages: 4-9

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Decreased protein C activation in patients with fulminant hepatic failure.2006

    • Author(s)
      Yamauchi M
    • Journal Title

      Scand J Gastroenterol 41

      Pages: 331-337

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Human protein C inhibitor gene transgenic mouse.2006

    • Author(s)
      Hayashi T, Suzuki K.
    • Journal Title

      Thrombosis and Circulation 13

      Pages: 4-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Decreased protein C activation in patients with fulminant hepatic failure.2006

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

      Scand J Gastroenterol 41

      Pages: 331-337

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Activated protein C inhibits bronchial hyperresponsiveness and Th2 cytokine expression in mice.2004

    • Author(s)
      Yuda H
    • Journal Title

      Blood 103

      Pages: 2196-2204

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Regulation of carcinoma cell invasion by protein C inhibitor whose expression is decreased in renal cell carcinoma.2004

    • Author(s)
      Wakita T
    • Journal Title

      Int J Cancer 108

      Pages: 516-523

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Impairment of IL-12-dependent STAT2 nuclear translocation in a patient with recurrent Mycobacterium avium infection.2004

    • Author(s)
      Toyoda H
    • Journal Title

      J Immunol 172

      Pages: 3905-3912

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Characterization of a novel human protein C inhibitor (PCI) gene transgenic mouse useful for studying the role of PCI in physiological and pathological conditions.2004

    • Author(s)
      Hayashi T
    • Journal Title

      J Thromb Haemost 2

      Pages: 949-961

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Activated protein C inhibits bronchia 1 hytperresponsiveness and Th2 cytokine expression in mice.2004

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

      Blood 103

      Pages: 2196-2204

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of carcinoma cell invasion by protein C inhibitor whose expression is decreased in renal cell carcinoma.2004

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

      Int J Cancer 108

      Pages: 516-523

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Impairment of IL-12-dependent STAT4 nuclear translocation in a patient with recurrent Mycobacterium avium infection.2004

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

      J Immunol 172

      Pages: 3905-3912

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Characterization of a novel human protein C inhibitor (PCI) gene transgenic mouse useful for studying the role of PCI in physiological and pathological conditions.2004

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

      J Thromb Haemost 2

      Pages: 949-961

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Experimental treatment of human neuroblastoma using live-attenuated poliovirus.2004

    • Author(s)
      Toyoda H
    • Journal Title

      Int.J.Oncol. 24

      Pages: 49-58

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Regulation of carcinoma cell invasion by protein C inhibitor whose expression is decreased in renal cell carcinoma.2004

    • Author(s)
      Wakita T
    • Journal Title

      Int.J.Cancer 108

      Pages: 516-523

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Impairment of IL-12-dependent STAT4 nuclear translocation in a patient with recurrent Mycobacterium avium infection.2004

    • Author(s)
      Toyoda H
    • Journal Title

      J.Immunol. 172

      Pages: 3905-3912

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Characterization of a novel human protein C inhibitor (PCI) gene transgenic mouse useful for studying the role of PCI in physiological and pathological conditions.2004

    • Author(s)
      Hayashi T
    • Journal Title

      J.Thromb.Haemost. 2

      Pages: 949-961

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Thrombin inhibitor, argatroban, prevents tumor cell migration and bone metastasis.2004

    • Author(s)
      Asanuma K
    • Journal Title

      Oncology 67

      Pages: 166-173

    • Related Report
      2004 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi