Functional analysis of the two regulatory mechanism-epithelial mesenchymal transition and cell motility-on the process of tumor invasion
| Project/Area Number |
17390120
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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 |
Experimental pathology
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| Research Institution | Osaka Medical Center for Cancer and Cardiovascular Diseases Osaka Prefectural Hospital Organization |
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Principal Investigator |
ITOH Kazuyuki Osaka Medical Center for Cancer and Cardiovascular Diseases, Biology, Department Head, 研究所, 部長 (20301806)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIOKA Kiyoko Osaka Medical Center for Cancer and Cardiovascular Diseases, Biology, Chief Investigator, 研究所, 主任研究員 (40342993)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2006: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2005: ¥10,400,000 (Direct Cost: ¥10,400,000)
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| Keywords | cancer invasion / Rho / ROCK / IGF / SSX / cytoskeleton / siRNA / NASBA |
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| Research Abstract |
In order to develop the effective cancer invasion/metastatic target therapy, we have been working with two regulatory mechanism-epithelial mesenchymal transition and cell motility in this project. Our present results are following.
1.We extended our previous finding concerning small GTP binding protein Rho-and Rho associated kinase (ROCK) pathway to show the effective inhibition of mammalian breast cancer cells (BCCs) to invade brain using rat model study (2).
2.Collaborating with Prof. Yee, we have reported the insulin-like growth factor (IGF) signaling and Rho-ROCK pathway in BCC invasion (3).
3.Collaborating with Dr.Nishimura, we have reported the involvement of LIM kinase-cofilin pathway (actin polymerization regulator) for epidermal growth factor (EGF) receptor cycling in human BCCs (5).
4.We have mostly focused on the new target molecule SSX in tumor invasion. The SSX genes were originally identified as fusion partners to the SYT gene in human synovial sarcomas carrying a recurrent t
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(X;18) (p11.2;q11.2) chromosomal translocation. Using Nucleic Acid Sequence-Based Amplification (NASBA), we found that the level of expression positively correlated with clinical stage, especially the metastatic case present very high SSX expression (1). In order to examine the biological function of SSX, we made stable transfectants with wild type SSX using human osteosarcoma cell line, Saos-2, and human fibrosarcoma cell line, HT1080. The SSX transfectants promoted colony formation in soft agar and tumor formation in nude mice, but showed little change in growth rate in 2D culture. The transfectants also increased motility, chemotaxis and invasiveness using Boyden chamber assay. By contrast, the lowering of the endogenous expression of SSX in HT1080 cells and Saos-2 cells by the treatment with specific siRNA markedly decreased chemotaxis and invasiveness and decreased cellular proliferation in 3D collagen gel culture. We also evaluated the efficacy of siRNA using Xenograft model in nude mice. Less
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Report
(3 results)
Research Products
(23 results)
