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2001 Fiscal Year Final Research Report Summary

Experimental research for the availability of gene therapy using ORP150, a novel molecular chaperone

Research Project

Project/Area Number 12671522
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionGRADUATE SCHOOL OF MEDICINE, KANAZAWA UNIVERSITY

Principal Investigator

OGAWA Satoshi  INSTITUTION, DEPARTMENT, TITILE OF POSITION Kanazawa Univ. Graduate school of Med, Professor, 医学系研究科, 教授 (90283746)

Co-Investigator(Kenkyū-buntansha) YOKOYAMA Osamu  Kanazawa Univ. Graduate school of Med, Assoc.Professor, 医学部・附属病院, 講師 (90242552)
KOSHIDA Kiyoshi  Kanazawa Univ. Graduate school of Med, Assoc.Professor, 医学系研究科, 助教授 (70186667)
Project Period (FY) 2000 – 2001
KeywordsStress response / Unfolded protein response / angiogenesis / Molecular chaperone / Gene therapy / Adenovirus vecto / Tumor growth
Research Abstract

Newly synthesized protein and immature proteins are easily aggregated because they ej(pose hydrophobic regions. Many stress conditions, such as heat shock or hypoxia, slow down their folding process and cause accumulation of unfolded/misfolded proteins in the cell. Molecular chaperones, including heat shock'proteins (IISPs), are induced in these conditions, bind to unfolded/misfolded proteins, and help them to be folded or reflolded properly. The protective role of molecular chaperones for the cells under stress has been reported.
Expression of angiogenic factors such as vascular endothelial growth factor (VEGF) under conditions of cell stress involves both transcriptionaland translational events, as well as an important role for inducible endoplasmicreticulum (ER) chaperones. Coexpression of VEGF and 150-kDaoxygen-regulated protein (ORP), a novel ER chaperone, in human glioblastomasuggested a link between angiogenesis and ORP150. C6 gliomacells stably transfected with ORP150 antisense … More displayed selectively reduced ORP150 expression. Tumors raised after in culation of immunocompromisedmice with ORP150 antisense C6 glioma transfectants demonstratedan initial phase of growth comparable to wild-type C6 gliomacells which was followed by marked regression within 8 days. Decreaseddensity of platelet/endothelial cell adhesion molecule 1-positive structureswithin the tumor bed was consistent with reduced angiogenesis in C6 gliomas expressing ORP150 antisense, compared with tumors derived from C6 cells overexpressing ORP150 sense or vector controls. In vitro,inhibition of ORP150 expression decreased release of VEGF into culturesupernatants ; in ORP150 antisense transfectants, VEGF accumulatedintracellularly within the ER. These findings demonstrate a critical rolefor the inducible ER chaperone ORP150 in tumor-mediated angiogenesisvia processing of VEGF, and, thus, highlight a new facet of angiogenicmechanisms amenable to therapeutic manipulation in tumors.
Heat shock proteins (HSPs)/stress proteins are molecular chaperflnes that are induced by various environmental and physiological stimuli. Evidence of the relations between the expression of HSPs and the regulation of cell growth or transformation has accumulated. The 150-kDa oxygen-regulated protein (ORP150), a new member of lisp family, functions as a molecular chaperone in the endoplasmic reticulum. We have examined whether transduced antisense ORP150 cDNA reduces tumorigenicity and angiogenicity. Relations between these stress proteins and cancer and possibilities for anticancer gene therapy are described. Less

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Tamatani他: "ORP 150 protects against hypoxia/ischemia-induced neuronal death"Nature Med.. 7. 317-323 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsukamoto他: "Expression of a novel RNA splicing factor, RA301/Tra2beta, in vascular lesions and its role in smooth muscle cell proliferation"Am. J. Pathol.. 158. 1685-1694 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ozawa他: "Regulation of tumor angiogeensis by ORP150, an inducible endoplasmic reticulum chaperone"Can. Res.. 61. 4206-4213 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ozawa他: "Expression of ORP150 (150 kDa Oxygen Regulated Protein) accelerates wound healing by modulating intracellular VEGF transport"J. Clin. Invest.. 108. 41-50 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kitao他: "Expression of 150 kDa Oxygen Regulated Protein (ORP150), a Molecular Chaperone in the Endoplasmic Reticulum, Rescues Hippocampal Neurons from Glutamate Toxicity"J. Clin. Invest.. 108. 291-299 (2001)

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      「研究成果報告書概要(和文)」より
  • [Publications] Miyagi他: "Antitumor Effect of Reduction of 150-kDa Oxygen-Regulated Protein Expression in Human Prostate Cancer Cells"Mol. Urol.. 5. 79-80 (2001)

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      「研究成果報告書概要(和文)」より
  • [Publications] Kobayashi T, Ogawa S, Yura T, Yanagi H.: "Abundant expression of 150-kDa oxygen-regulated protein in mouse pancreatic beta cells is correlated with insulin secretion."Biochem. Biophys. Res. Commun.. 267. 831-837 (2000)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Bando Y, Ogawa S, Yamaguchi A, Kuwabara K, Ozawa K, Hori O, Yanagi H, Tamatani M, and Tohyama M.: "The 150 kDa Oxygen Regulated Protein (ORP150 functions as a novel molecular chaperone in the protein transport of the MDCK cells."Am. J. Physiol. (Cell Pysiol.). 278, (6). C1172-1182 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] amatani M, Matsuyama T, Yamaguchi A, Mitsuda N, Tsukamoto Y, Taniguchi T, Che YH, Ozawa K, Hori O, Nishimura H, Yamashita A, Okabe M, Yanagi H, Stern DM, Ogawa S, and Tohyama M.: "ORP150 protects against hypoxia/ischemia-induced neuronal death."Nature Med.. 7. 317-323 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsukamoto Y, Matsuo N, Ozawa K, Hori O, Higashi T, Nishizaki J, Tohnai N, Nagata I< Kawano K, Yutani C, Hirota S, Kitamura Y, Stern D, and Ogawa S.: "Expression of a novel RNA splicing factor, RA301/Tra2beta, in vascular lesions and its role in smooth muscle cell proliferation."Am. J. Pathol. 158. 1685-1694 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ozawa K, Tsukamoto Y, Hori O, Kitao Y, Yanagi Stern D, and Ogawa S.: "Regulation of tumor angiogeensis by ORP150, an inducible endoplasmic reticulum chaperone."Can. Res.. 61. 4206-4213 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ozawa K, Kondo T, Hori O, Kitao Y, Stern D, Eisenmenger W, Ogawa S, and Ohsima T.: "Expression of ORP150 (150 kDa Oxygen Regulated Protein) accelarates wound healing by modulating intracellular VEGF transport."J. Clin. Invest.. 108. 41-50 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sato M, Sugano N, Ohzono K, Nomura S, Kitamura Y, Tsukamono Y, Ogawa S.: "Apoptosis and expression of stress protein (ORP150, HO1) during development of ischaemic osteonecrosis in the rat."J Bone Joint Surg Br.. 83. 751-759 (2001)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Vorp DA, Lee PC, Wang Dh, Makaroun MS, Nemoto EM, Ogawa S, and Webster MW.: "Association of intraluminal thrombus in abdominal aortic aneurysm with local hypoxia and wall weakening."J Vasc Surg. 34. 291-299 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kitao Y., Ozawa K., Miyazaki M., Kobayashi T., Yanagi H., Okabe M., Ikawa M., Yamashima T., Tohyama M., Stern D., Hori O., and Ogawa S.: "Expression of 150 kDa Oxygen Regulated Protein (ORP150), a Molecular Chaperone in the Endoplasmic Reticulum, Rescues Hippocampal Neurons from Glutamate Toxicity."J. Clin. Invest.. 108. 1439-1450 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] iyagi T, O, Egawa M, Kato H< Kitagawa Y, Konaka H, Ozawa K, Koshida K, Uchidayashi T, Ogawa S, and Namiki M.: "Antitumor Effect of Reduction of 150-kDa Oxygen-Regulated Protein Expression in Human Prostate Cancer Cells."Mol. Urol.. 5. 79-80 (2001)

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      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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