2000 Fiscal Year Final Research Report Summary
Establishment of inflammatory and malignant tumor disease model mice based on abnormalities in adhesiveness of immune cells and its clinical application.
| Project/Area Number |
11557011
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Kobe University |
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Principal Investigator |
MINAMI Yasuhiro Kobe University, School of Medicine, Professor, 医学部, 教授 (70229772)
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| Co-Investigator(Kenkyū-buntansha) |
IIGO Yutaka Daiichi Pharmaceutical Co., Ltd., New Product Research Laboratories IV.Associate Senior Researcher, 創薬第四研究所, 副主任研究員
TANAKA Yoshiya University of Occupational and Environmental Health, School of Medicine, Professor, 医学部, 教授 (30248562)
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| Project Period (FY) |
1999 – 2000
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| Keywords | lymphocytes / proto-oncogenes / H-Ras / c-Myc / cell adhesion / Integrins / gene expression / anti-oncogene |
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| Research Abstract |
In this study we found that in mouse pro-B cell line, BAF-B03 cells, an active form of H-Ras activates α_4 and α_6 integrins, thereby enhancing cell adhesiveness to fibronectin and laminin. It was also found that functional cooperation of an active form of H-Ras and c-Myc results in the activation of α_4 integrin, the induction of VCAM-1, a counter-receptor for VLA-4 (α_4β_1), and in the down-regulation of α_6a integrin, leading to homophilic cell aggregation and to a loss of cell adhesiveness to laminin. Furthermore, it was shown that BAF-B03 cells constitutively expressing an active form of H-Ras and c-Myc form tumor and exhibit invasion and metastasis when injected into nude mice. Loss of laminin binding of BAF-B03 cells expressing active H-Ras and c-Myc may contribute to infiltration of tumor cells from primary nodules. It would be of interest to examine whether or not functional cooperation of H-Ras and c-Myc in regulating the expression and/or activity of cell adhesion molecules is cell-type specific. In this study, we also showed that synovial cells from patients of Rheumatoid Arthritis (RA) can be separated into two functionally distinct subsets on the basis of the expression levels of ICAM-1. ICAM-1-positive cells exhibit cell cycle arrest and undergo apoptosis, while ICAM-1-negative cells proliferate efficiently and continuously. It is assumed that ICAM-1-negative synovial cells in RA patients can be an important therapeutic target.
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Research Products
(15 results)
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[Publications] Liu, Z-J., Tanaka, Y., Fujimoto, H., Mine, S.Morinobu, A., Yagita, H., Okumura, K., Oishi, I., Udagawa, J., Yamamura, H., and Minami, Y.: "A novel role for H-Ras in the regulation of VLA-4 integrin and VCAM-1 via c-Myc-dependent and -independent mechanisms."J.Immunol.. 163. 4901-4908 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Tanaka, Y., Minami, Y., Mine, S., Hirano, H., Fujimoto, H., Fujii, K., Saito, K, Tsukada, J., van Kooyk, Y., Figdor, C.G., Kataoka, T., and Eto, S.: "H-Ras signals to cytoskeletal machinery in induction of integrin-mediated adhesion of T cells."J.Immunol.. 163. 6209-6216 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Tanaka, Y., Maruo, A., Fujii, K., Nomi, M., Nakamura, T., Eto, S., and Minami, Y.: "ICAM-1 discriminates functionally different populations of human osteoblasts : characteristic involvement of cell cycle regulators."J.Bone Mineral Res.. 15. 1912-1923 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Tanaka, Y., Nomi, M., Fujii, K., Hubscher, S., Maruo, A., Awazu, Y., Sito, K, Eto, S., and Minami, Y.: "ICAM-1 distinguishes functional heterogeneity of synovial cells in patients with rheumatoid arthritis : involvement of cell cycle machinery."Arthritis Rheum.. 43. 2513-2522 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Oishi, I., Iwai, K., Kagohashi, Y., Fujimoto, H., Kariya, K., Kataoka, T., Sawa, H., Okano, H., Otani, H., Yamamura, H., and Minami, Y.: "Critical role of a C.elegans homolog of Cds1/Chk2-related kinase, Ce-CDS-1, in meiotic recombination."Mol.Cell.Biol.. 21. 1329-1335 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Fujimoto, H., Tanaka, Y., Liu, Z-J., Yagita H., Okumura, K., Kosugi, A., Morinobu, A., Yamamura, H., and Minami, Y.: "Down-regulation of α_6 integrin, an antioncogene product, by functional cooperation of H-Ras and c-Myc."Genes to Cells. (in press). (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Minami, Y., Qin, S., Hibi, M., Kurosaki, T., and Yamamura, H.: "Redox Regulation of Cell Signaling and its Clinical Applications"Marcel Dekker Inc.NY, USA. 8 (1998)
Description
「研究成果報告書概要(欧文)」より
