| Project/Area Number |
13670563
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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 |
Gastroenterology
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| Research Institution | TOKYO DENTAL COLLEGE |
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Principal Investigator |
NAKANO Masaru TOKYO DENTAL COLLEGE, DEPARTMENT OF DENTISTRY, ASSISTANT, 歯学部, 助手 (50265807)
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| Co-Investigator(Kenkyū-buntansha) |
HIBI Toshihumi KEIO UNIVERSITY, SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (50129623)
AZUMA Toshihumi KEIO UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT00222612, 医学部, 助手 (00222612)
NISHIDA Jirou TOKYO DENTAL COLLEGE. DEPARTMENT OF DENTISTRY, PROFESSOR, 歯学部, 教授 (50198470)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | colon cancer / metastasis / Racl / Rho-fatnily GTPases / GTP-bindinK protein |
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| Research Abstract |
It is well accepted that cancer cells are biologically heterogeneous and metastatic capability is one of the most prominent heterogeneous property of cancer cells. Recent progress revealed that cancer cell motility, which is quite different from cell to cell, plays a central role in a tumor metastasis. Initial step of cell migration is extension of active membrane processes, including both lamellipodia and filopodia, which takes place primarily around cell front with cell locomotion taking on a persistent random walk. Assembly of actin filament drives the locomotion of tumor cells. Expansion of dense net work of action filaments underlying the plasma membrane provides sufficient force to push forward the leading edge. These processes are regulated Rho family GTPases. The basic signaling properties of two major subgroups of Rho GTPases-the Rac and Cdc42 sub families-are highlyconserved among alleukaryotes, but the means by which they act in cancer cell are not well understood. Recent evidence indicated that Rho activationplay some role in hepatoma and prostate cancer cell migration and invasion. Although cells transfected with active mutant Rac or Cdc42 CDNA in vitroacquired high motility, any cancer tissues or cell lines have not been found to have similar mutations in Rac or Cdc42 gene so that the roles of Racand Cdc42 sub families in cancer cells are not well understood. Here we report that some colon cancer cell lines maintains high GTP bound form Rac-active Rac-and high invasive ability. Interestingly Rho activation which induces high motility of some hepatoma inhibited motility of those colon cancer cells with high active Rac. Another unexpected finding was that there were no significant differences in Cdc42 active state in colon cancer celllines. This finding indicates that Rac as well as Rho not cdc42 are the major Rho family GTPases to regulate colon cancer cell motility.
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