2002 Fiscal Year Final Research Report Summary
Studies on molecular mechanism of tumor suppression by the drs gene
| Project/Area Number |
13670211
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
INOUE Hirokazu Department of Microbiology, School of Medicine, Shiga University of Medical Science, Associate Professor, 医学部, 助教授 (30176440)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Tumor suppressor gene / Drs gene / Apoptosis / Knockout mouse |
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| 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
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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).
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「研究成果報告書概要(欧文)」より
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[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
