| Project/Area Number |
15390610
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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 | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | GIFU UNIVERSITY |
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Principal Investigator |
SHIBATA Toshiyuki GIFU UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFFESOR, 大学院・医学系研究科, 教授 (50226172)
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| Co-Investigator(Kenkyū-buntansha) |
HAMADA Junichi HOKKAIDO UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSOCIATED PROFFESOR, 大学院・医学研究科, 助教授 (50192703)
TOIDA Makoto GIFU UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSOCIATED PROFFESOR, 大学院・医学系研究科, 助教授 (90313890)
YAMASHITA Tomomi GIFU UNIVERSITY, UNIVERSITY HOSPITAL, ASSISTANT PROFFESOR, 医学部附属病院, 講師 (80345793)
MAKITA Hiroki GIFU UNIVERSITY, UNIVERSITY HOSPITAL, RESEARCH ASSOCIATE, 医学部附属病院, 助手 (50345790)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥13,800,000 (Direct Cost: ¥13,800,000)
Fiscal Year 2005: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2004: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2003: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Keywords | SCC / HUMAN / EGF / INVASION / EGF RECEPTOR / PKC |
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| Research Abstract |
Our previous studies revealed that EGF enhanced the random motility of oral squamous cell carcinoma cell lines in a dose-dependent fashion and exposure to EGF let to an increased production of urokinase type plasminogen activator and matrix metalloproteniase-9 by the same cells. These results strongly suggest the EGF may promote the invasion and metastasis of human oral squamous cell carcinomas. In this project, to reveal the signal pathway concerning the cell motility and inhibiting effects of signal pathway, we established s-1 clone cells from Ca9-22 cell line, which was most sensitive clone against the EGF stimulation and also we established i-1 clone cells, which was most insensitive clone. Further studies were done using s-1 clone cells. When EGF bind to the EGF receptor, tyrosine phosphorelation is firstly occurred and subsequently PKC is activated through the activation of PLCr arising from erbB homodimer and/or activation of PI3-kinase arising from erbB3 heterodimer. Furthermore, erbB homodimer activates the nPKCd through the activation of PLC and also erbB/erbB-3 heterodimer activates aPKCe through the activation of PI3K. These results suggest that inhibition of aPKCe or nPKCd can reduce the invasion and metastasis of human oral cancer cells and that the useful model in the investigations of molecular target medicines is possibly established. Furthermore, as an auspicious candidate of new target molecules, aPKCe and nPKCd were closed up. Especially, these molecles were more specific than EGF receptor, PI3K, and so on, which recently developed molecular target medicines.
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