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

温熱で誘導される分子シャペロンを利用したがん治療法の開発

Research Project

Project/Area Number 12217171
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionChubu University (2001-2004)
Aichi Cancer Center Research Institute (2000)

Principal Investigator

大塚 健三  中部大学, 応用生物学部, 教授 (40150213)

Co-Investigator(Kenkyū-buntansha) 中村 普武  愛知県がんセンター, 腫瘍ウィルス学部, 室長 (30109938)
Project Period (FY) 2000 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥39,200,000 (Direct Cost: ¥39,200,000)
Fiscal Year 2004: ¥8,300,000 (Direct Cost: ¥8,300,000)
Fiscal Year 2003: ¥8,100,000 (Direct Cost: ¥8,100,000)
Fiscal Year 2002: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2001: ¥8,600,000 (Direct Cost: ¥8,600,000)
Fiscal Year 2000: ¥7,000,000 (Direct Cost: ¥7,000,000)
Keywords分子シャペロン / Hsp70 / Hsp40 / 温度感受性変異株 / シャペロン誘導剤 / ペオニフロリン / 抗腫瘍効果 / 遺伝子病治療 / アポトーシス / HSF1 / 温度感受性変異蛋白質 / 遺伝病治療
Research Abstract

1.熱ショック蛋白質(heat shock protein、HSP)はさまざまな環境ストレスで誘導される。HSPは分子シャペロンとして機能し、細胞内の種々の機能を制御しているだけでなく、タンパク質毒性をもつストレスに対する内因性の防御因子でもある。毒性のない薬剤などでこの分子シャペロンを誘導できれば、生体はさまざまな環境ストレスに対して抵抗性になると考えられている。そこで漢方薬のなかで分子シャペロン誘導剤がないかどうかをスクリーニングしたところ、ペオニフロリンという化合物がそれ単独でも熱ショック転写因子(HSF1)を活性化し、Hsp70、Hsp40、Hsp27などを誘導することが判明した。またペオニフロリンで処理した細胞は温熱耐性を獲得し、さらにマウスにおいても塩酸による胃潰瘍の発生がペオニフロリン前投与により抑制された。ペオニフロリンを投与したマウスではB16メラノーマ細胞の増殖が抑制された。今後は線虫を用いた寿命延長効果などについても検討する。さらのこれ以外の分子シャペロン誘導剤の探索も行う。
2.突然変異により温度感受性(39℃では増殖不能)になった細胞(tsTM4)に分子シャペロンを導入し、分子シャペロンが変異蛋白質の機能を回復させることができるかどうかを検討した。構成的に活性型となったHSF1を導入したところ39℃でも増殖できる細胞が出現してきた。このことは分子シャペロンが過剰に存在すると、変異蛋白質であっても正常に機能できることを示唆している。
3.瘍性大腸炎におけるHsp40の自己抗体について検討した。26例の潰瘍性大腸炎患者のうち17例について炎症部位においてHsp40が発現しており、同時にCD68も発現していた。潰瘍性大腸炎患者の血清中には抗Hsp40抗体が検出された。重症の患者より軽傷の患者において抗Hsp40抗体の力価が高かった。このことからHsp40の自己抗体は潰瘍性大腸炎患者にとって有益な効果を持っていることが示唆された。

Report

(5 results)
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (23 results)

All 2004 Other

All Journal Article (4 results) Publications (19 results)

  • [Journal Article] Autoimmunity to heat shock protein 40 in ulcerative colitis.2004

    • Author(s)
      Sato, S.
    • Journal Title

      J.Int.Med.Res. 32

      Pages: 141-148

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Reinvestigation of the requirement of cytosolic ATP for mitochondrial protein import.2004

    • Author(s)
      Asai, T.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 19464-19471

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Paeoniflorin, a novel heat shock protein-inducing compound.2004

    • Author(s)
      Dai, Y.
    • Journal Title

      Cell Stress & Chaperones 9

      Pages: 378-389

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Formation of aggresome-like structures in herpes simplex virus type 2-infected cells and a potential role in virus assembly.2004

    • Author(s)
      Nozawa, N.
    • Journal Title

      Exp.Cell Res. 299

      Pages: 486-497

    • Related Report
      2004 Annual Research Report
  • [Publications] Ohtsuka, K.: "Hsp105alpha suppresses the aggregation of truncated androgen receptor withexpanded CAG repeats and cell toxicity."J.Biol.Chem.. 278. 25143-25150 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohtsuka, K.: "Expression of heat shock protein (Hsp) 70 and Hsp40 in colorectal cancer."Medical Oncol.. 20. 157-164 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohtsuka, K.: "Expression of heat shock protein (Hsp) 70 and Hsp40 in gastric cancer."Cancer Lett.. 198. 219-226 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohtsuka, K.: "Heat-shock protein 70 binds caspase-activated DNase and enhances its activity in TCR-stimurated T cells."Blood. 102. 1788-1796 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohtsuka, K.: "Re-investigation of the requirement of cytosolic ATP for mitochondrial protein import."J.Biol.Chem.2004.. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohtsuka, K.: "Hsp70 and Hsp40 improve neurite outgrowth and suppress intracytoplasmic aggregate formation in cultured neuronal cells expressing mutant SOD1"Brain Res.. 949. 11-22 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohtsuka, K.: "Herpes simplex virus type 2 UL14 gene product has heat shock protein (HSP)-like functions"J. Cell Sci.. 115. 2517-2527 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohtsuka, K.: "Phosphorylation of cytoskeleton 17 by Herpes simplex virus type 2 US3 protein kinase"Microbial. Immunol.. 46. 709-719 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohtsuka, K.: "Heat-shock protein 70 binds caspase-activated DNase and enhances its activity in TCR-stimurated T cells"Blood. (In Press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohtsuka, K.: "Autoantibody to heat shock protein Hsp4O of lung cancer patients"Jpn. J. Cancer Res.. 92. 316-320 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohtsuka, K.: "Characterization of a processed pseudogene of human ΨHSP4O on chromosome 2q32"DNA Sequence. 12. 293-297 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohtsuka, K.: "Hsp70 and Hsp40 improve neurite outgrowth and suppress intracytoplasmic aggregate formation in cultured neuronal cells expressing mutant SOD 1"Brain Res.. (In press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohtsuka,K.: "Roles of molecular chaperones in the nervous system."Brain Res.Bull.. 53. 141-146 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohtsuka,K.: "Identification of Mrj, a DnaJ/Heat shock protein 40 family protein, as a keratin 8/18 filament-regulatory prolein."J.Biol.Chem.. 275. 34521-34527 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohtsuka,K.: "Mammalian HSP40/DNAJ homologs : Cloning of novel cDNAs and a proposal for their classification and nomenclature."Cell Stress & Chaperones. 5. 98-112 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohtsuka,K.: "Chaperones, Hsp70 and Hsp40, suppress aggregate formation and apoptosis in cultured neuronal cells expressing truncated androgen receptor protein with expanded polyglutamine tract."J.Biol.Chem.. 275. 8772-8778 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohtsuka,K.: "Cloning and expression of murine Hsp40 gene : Differences in initiation sites between heat-induced and constitutive transcript."DNA Seq.. 11. 213-223 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohtsuka,K.: "Molecular chaperone function of mammalian Hsp70 and Hsp40-A review."Int.J.Hyperthermia. 16. 231-245 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohtsuka,K.: "Thermotherapy for Neoplasia, Inflammation, and Pain"Kosaka,M.,Sugahara,T.,Schmidt,K.L.and Simon,E.(Eds). 550 (2000)

    • Related Report
      2000 Annual Research Report

URL: 

Published: 2000-04-01   Modified: 2018-03-28  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi