1997 Fiscal Year Final Research Report Summary
Studies on suppression of transformation in primary rat embryo fibroblasts
Project/Area Number |
07670244
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Experimental pathology
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Research Institution | Osaka University |
Principal Investigator |
INOUE Hirokazu Res.Inst.for Microbial Dis., Osaka University, Research Assosiate, 微生物病研究所, 助手 (30176440)
|
Project Period (FY) |
1995 – 1997
|
Keywords | Transformation / Oncogene / Tumor suppressor gene / Primary cells / Colon cancer |
Research Abstract |
On searching for transformation suppressor genes in primary cells, we isolated a novel gene, drs (doenregulated by v-src), which was expressed in normal rat fibroblast cells but completely suppressed in the cells transformed by the v-src gene, from a cDNA library of REF.The molecular cloned cDNA was about 1.8kb in size, containing an open reading frame composed of 464 amino acid residues. Homology search of drs protein revealed that this protein had one transmembrane domain and three consensus repeats (CR) which were conserved as various numbers of CR in extracellular domain of the selsctin family. Expression of drs mRNA was also down-regulated by serum stimulation of G0-arrested normal rat cells. To clarify the biological function of the drs gene, we introduced the drs gene linked to potent promoter into normal rat cell line and examined the sensitivity to transformation by the v-src oncogene. Rat cell lines expressing exogenous drs gene showed lower efficiency of v-src transformation, indicating a transformation suppressor function of the drs gene. The drs gene was also downregulated in human colon cancer cell lines and ectopic expression of this gene suppressed the ability of prolifelation in these cancer cell lines, suggesting a role in the genesis of human cancers.
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[Publications] Shimakage, M., Kurata., A., Inoue, H., Okamoto, Y., Yutsudo, M., and Hakura, A.: "Tumorigenicity of EBNA2-transfected cells." FEBS letters. 371. 245-248 (1995)
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「研究成果報告書概要(欧文)」より
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[Publications] Pan, J., Nakanishi, K., Yutsudo, M., Inoue, H., Li, Q., Oka, K., Yoshioka, N., and Hakura, A.: "Isolation of a novel gene down-regulated by v-src." FEBS letters. 383. 21-25 (1996)
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「研究成果報告書概要(欧文)」より
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[Publications] Tang, G., lida, T., Inoue, H., Yutsudo, M., Yamamoto, K., and Honda, T.: "A mutant cell line resistant to Vibrio parahaemolyticus thermostablle direct hemolysin (TDH) : its potential in identification of putative receptor for TDH." Biochim.Biophys.Acta. 1360. 277-282 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Matsumoto, K., Fujisawa, J., Inoue, H., Hakura, A., Shibata, H., and Fujii, M.: "Human T-cell leukemia virus type I tax protein transforms rat fibroblasts via two distincitive pathways." J.Virol.71. 4445-4451 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Ishiwatari, H., Nakanishi, K., Kondoh, G., Hayasaka, N., Li, Q., Yamashita, A., Inoue, H., and Hakura, A.: "Suppression of tumor growth by the 3'untranslated region of mel-18 in 3Y1 cells transformed by the E6 and E7 genes of human papillomavirus type 18." Cancer letters. 117. 57-65 (1997)
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「研究成果報告書概要(欧文)」より
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