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Studies on molecular mechanism of tumor suppression by the drs gene

Research Project

Project/Area Number 13670211
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionShiga University of Medical Science

Principal Investigator

INOUE Hirokazu  Department of Microbiology, School of Medicine, Shiga University of Medical Science, Associate Professor, 医学部, 助教授 (30176440)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsTumor suppressor gene / Drs gene / Apoptosis / Knockout mouse / がん抑制遺伝子 / drs遺伝子
Research Abstract

The drs gene was originally isolated as a suppressor gene against v-src transformation. We have shown that expression of drs mRNA was markedly reduced in a variety of human cancer cell lines, and introduction of drs cDNA by retrovirus vector into these cancer cell lines caused suppression of anchorage-independent growth. These findings indicate that downregulation of drs mRNA is closely correlated with expression of malignant phenotype in development of human cancers and the drs gene act as a tumor suppressor. In this project, we performed the research to clarify the mechanism of tumor suppression by the drs gene and obtained the following results.
1. Identification of Drs-binding proteins
We have established the systems to identify Drs-binding proteins by immunoprecipitation and peptide mass fingerprinting methods in cells expressing high level of Drs protein. By using these systems, we found that several cellular proteins including GRF78/BiP and α-glucosidase-α subunit are associated w … More ith Drs.
2. Construction and analysis of drs-knockout mouse
By gene-targetting techniques, we succceeded in making germ line-transmitted drs kockout mouse. Analyses of Drs KO mouse on tumor formation and physiological function of the drs gene are in progress.
3. Investigation of correlation between expression of malignant phenotypes and downregulation of drs gene in human cancers
To clarify the role of the drs gene in the development of human cancers, we examined the expression of the drs mRNA and the status of genome DMA of drs in normal, benign, and malignant tissues of colon, lung, prostate cancers and lymphomas of ATL We found that drs mRNA was downregulated in malignant tissues of these cancers. Neither gross deletion nor rearrangement of the drs genome was detected in these malignant tissues.
4. Apotosis-inducing activity of drs.
Wefound that drs can induce apoptosis by activation of caspase-12, -9-, -3 in human cancer cell lines, suggesting a novel apoptosis-mediated pathway of tumor suppression by the drs gene. Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Q.Li et al.: "Link of a new type of apoptosis -inducing gene ASY/Nogo-B to human cancer"Oncogene. 20. 3929-3936 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.Kuwai et al.: "Isolation of a novel mouse variant of the drs tumor suppressor gene"Cancer Letters. 183. 79-86 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Shimakage et al.: "Expression of drs m RNA in human lung adenocarcinomas"Human Pathology. 33. 615-619 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Mukaisho et al.: "Down-regulation of drs mRNA in colorectal neoplasms"Jap. J. Cancer Res.. 93. 888-893 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N.Yoshioka et al.: "Suppression of anchorage -indepencent growth of human cancer cell lines by the TRIF52/periostin/OSF-2 gene"Exp. Cell Res.. 279. 91-99 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] B.Qi et al.: "Pro-apoptotic ASY/Nogo-B protein associates with ASYIP"J. Cell. Physiol.. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] C.J.Kim et al.: "Down-regulation of drs mRNA in human prustate caricinomas"Human Pathology. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Li,Q., Oka,K., Shimakage,M., Yoshioka,N., Kodama,K., Inoue,H., Hakura,A., Stanbridge,E.J., and Yutsudo,M.: "Link of a new type of apoptosis-inducing gene ASY/Nogo-B to human cancer"Oncogene. 20. 3929-3936 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawai,T., Suzuki,Y., Yamashita,A., and Inoue,H.: "Isolation of a novel mouse variant of the drs tumor suppressor gene"Cancer Letters. 183. 79-86 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimakage,M., Takami,K., Kodama,K., Mario,M., Yutsudo,M. and Inoue,H.: "Expression of drs mRNAin human lung adenocarcinomas"Human Pathology. 33. 615-619 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mukaisho,K., Suo,M., Shimakage,M., Kushima,R., Inoue,H., and Hattori,T.: "Down-regulation of drs mRNA in colorectal neoplasms"Jap.J.Cancer Res.. 93. 888-893 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshioka,N., Fuji,S., Shimakage,M., Kodama,K., Hakura,A., Yutsudo,M., Inoue. H., and Nojima,H.: "Suppression of anchorage-independent growth of human cancer cell lines by the TRIF52/periostin/OSF-2 gene"Exp.Cell Res.. 279. 91-99 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Qi,B., Qi,Y., Watari,A., Yoshioka,N., Inoue,H., Minemoto,Y., Yamashita,K., Sasagawa,T.and Yutsudo,M.: "Pro-apoptotic ASY/Nogo-B protein associates with ASYIP"Journal of Cellular Physiology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kim,C.J., Shimakage,M., Kushima,R., Mukaisho,K., Shinka,T., Okada,Y. and Inoue,H.: "Down-regulation of drs mRNA in human prostate carcinomas"Human Pathology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.Kawai et al.: "Isolation of a novel mouse variant of the drs tumor suppressor gene"Canner Letters. 183. 79-86 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M.Shimakage et al.: "Expression of drs mRNA in human lung adenocarcinomas"Human Pathology. 33. 615-619 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Mukaisho et al.: "Down-regulation of drs mRNA in colorectal neoplasms"Jap. J. Cancer Res.. 93. 888-893 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] N.Yoshioka et al.: "Suppression of anchorage-independent growth of human cancer cell lines by the TRIF52/periostin/OSF-2 gene"Exp. Cell. Res.. 279. 91-99 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] B.Qi et al.: "Pro-apoptotic ASY/Nogo-B protein associates with ASYIP"J. Cell. Physiol.. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] C.J.Kim et al.: "Down-regulation of drs mRNA in human prostate carcinomas"Human Pathology. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Kawai et al.: "Isolation of a novel mouse variant of the drs tumor suppressor gene"Cancer Letters. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Q.Li et al.: "Link of a new type of apoptosis-inducing gene ASY/Nogo-B to human cancer"Oncogene. 20. 3929-3936 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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