1996 Fiscal Year Final Research Report Summary
Investigation of transforming activity of cyctatin which has a similarity to Ras
| Project/Area Number |
07808084
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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 |
Cell biology
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| Research Institution | Chiba Cancer Center Research Institute |
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Principal Investigator |
HIWASA Takaki Chiba Cancer Center Research Institute, 研究局・生化学研究部, 研究員 (30260251)
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| Project Period (FY) |
1995 – 1996
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| Keywords | ras / cysteine proteinase / cystatin / transformation |
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| Research Abstract |
We have found a potent cysteine proteinase inhibitory activity of ras gene product (Ras). To elucidate whether the protease-inhibitory activity of Ras is involved in carcinogenesis, the present study was carried out using the following probes ; (gene 1) cyctatin which hasa similar cysteine proteinase-inhibitory activity but no GTP-binding activity, (gene 2) cystatin which has a CAAX motif of Ras at the carboxy-terminus, (gene 3) RasDELTA42-49 which has a deletion between amino acide 42 and 49 and retains the cysteine proteinase-inhibitory activity but has completely lost GTP-binding activity. These genes were transfected into NIH3T3 cells and the transfected cells were isolated. The expression of the introduced genes were effectively induced by treatment with dexamethasone. Then, the colony-forming ability in soft agar medium was investigated in the presence of dexamethasone. The results showed that cells were not transformed by expression of these genes. However, high colony-forming efficiencies were observed after induction of genes 2 or 3 in the presence of a tumor promoter, TPA,suggesting that the cells were anchorage-independently transformed.Induction of gene 1 resulted in a moderate increase in the colony-forming abilty. These results suggest that suppression of cycteine proteinases induces an initial chage in carcinogenesis.
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[Publications] Hiwasa, T., Soeda, C., Takanohashi, S., Kobayashi, H.Suzuki, A., Ueyama, T., and Ike, Y.: "Screening of peptides which suppress the proliferation of transformed cells." Int. J.Oncol.8. 125-129 (1996)
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「研究成果報告書概要(欧文)」より
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[Publications] Hiwasa, T., Tokita, H., Hirose, M., Ike, Y., and Ohkoshi, M.: "Enhancement of anti-proliferative activities of 5-FU,HCFU,SN-38, THP and ACNU by a serine protease inhibitor, FOY-305." Int. J.Oncol.9. 517-520 (1996)
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「研究成果報告書概要(欧文)」より
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