| Project/Area Number |
13470254
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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 |
Digestive surgery
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
DOI Ryuichiro Kyoto University, Surgery and Surgical Basic Science, Assistant Professor, 医学研究科, 講師 (20301236)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIMOTO Koji Kyoto University, Surgery and Surgical Basic Science, Instructor, 医学研究科, 助手 (70335280)
IMAMURA Masayuki Kyoto University, Surgery and Surgical Basic Science, Professor, 医学研究科, 教授 (00108995)
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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 |
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 2002: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2001: ¥4,300,000 (Direct Cost: ¥4,300,000)
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| Keywords | TGF-β / epithelial mesenchymal transition / Smad / cadherin / RhoB / 膵癌 / 浸潤 / 転移 |
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| Research Abstract |
[TGF-β signal and Function of RhoB protein] We induced epithelial mesenchymal transition (EMT) in the cultured cell by TGF-β stimulation. In addition, we found the relation between EMT and invasiveness of the cells stimulated by TGF-β. We also found that the protein and mRNA expression of RhoGTPases was suppressed in TGF-β signaling. Stable clones were established by using wild-type and mutant-type of RhoB expression vectors in order to analyze RhoB protein function. We examined, in these cells, the induction of EMT, cell proliferation, anchorage-independent cell proliferation, migration and invasion. The TGF-β stimulation signal pathway is thought to be chiefly composed of Smad signal pathway and MAPKs cascade (ERK1/2, JNK/SAPK and p38MAPK). We showed that the signal pathway which related to invasion and metastasis is MAPKs cascade. [Alteration of oncogene and invasion and metastasis in pancreatic cancer] We used pancreatic cancer cell lines with the different status of K-Ras, DPC4 and to TGF-βRII gene mutation. Stable clone with DNRas was established. Stable clones with DN and CA form of RhoB, MEK1/2 and SMAD4 were also established. The ability of invasion and metastasis stimulated by TGF-β was examined by using these cells. Moreover, the state of EMT, and the expression of RhoB protein, Cdc42 and cadherin were examined in response to the TGF-β stimulation. We showed alteration of TGF-β signaling and increased invasion and metastasis by enforced activation of Ras protein. We finally confirmed alteration of K-Ras and DPC4 in pancreatic cancer tissues.
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