| Project/Area Number |
16590242
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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 |
Pathological medical chemistry
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| Research Institution | Shinshu University School of Medicine |
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Principal Investigator |
KAMATA Tohru Shinshu University, School of medicine, professor, 医学部, 教授 (40056304)
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| Co-Investigator(Kenkyū-buntansha) |
ADACHI Yoshifumi Shinshu University, School of medicine, Associated professor, 医学部, 助教授 (50201893)
SHINOHARA Masahiro Shinshu University, School of medicine, Research Associate, 医学部, 助手 (60345733)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Nox1 / Ras / reactive oxygen species / redox signaling / cancer / pancreatic cancer / melanoma / Nox4 / MAP Kinase / 癌 / RNAi / MAPkinase / 転移 / 情報伝達 |
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| Research Abstract |
The aim of our study is to elucidate the functional role of reactive oxygen species (ROS) -generating Nox1 family genes in development of human cancers by utilizing Ras-transformation as a model system and lay a foundation for treatment and diagnosis of human cancers. We previously found that Ras oncogene upregulates Nox1 expression via Raf-MEK-MAPK pathway and Nox1 generated-ROS are required for oncogenic Ras transformation. This implicates an important role as a new limiting factor for Nox1 in oncogenesis. In the current study, we demonstrated that Nox4-generated ROS confer cell survival activity to pancreatic cancer cells through the AKT-ASK1 pathway and inhibit cell growth of melanoma cells by deregulating cell cycle. Furthermore, we identified ER proteins, PDI family proteins as potential downstream targets for Nox1-generated ROS whose Cys-SH residues are selectively oxidized by ROS. In the future study, we will further analyze what activity associated with these redox proteins is essential for Nox1-mediated cell transformation process. Our discovery accelerates the dissection of Nox-redox signaling pathway and provides a novel insight into its functional role in cancer development.
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