| Project/Area Number |
24590448
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Hokkaido University (2013-2014)
Sapporo Medical University (2012) |
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Principal Investigator |
TAMURA Yasuaki 北海道大学, フード&メディカルイノーべーション推進本部, 特任教授 (80322329)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 低酸素 / 酸化酵素 / 分子標的治療 / がんワクチン / MHC クラスI分子 / ジスルフィド結合 / ERO1-α / PDI / 腫瘍免疫 / G-CSF / MHC クラスI / VEGFA / 細胞周囲環境 / 免疫抑制性細胞 / がん幹細胞 / 乳がん / 上皮間葉転換 / がん抗原ペプチド / 細胞障害性T細胞 / 膵臓癌 / 大腸癌 / 乳癌 |
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| Outline of Final Research Achievements |
ERO1-α is an ER-resident oxidase. ERO1-α and PDI play a central role in disulfide bond formation of secreted and cell surface molecules. We have recently demonstrated that various types of tumor cells expressed high levels of ERO1-α. In this study, we show that ERO1-α associates with PDI, calnexin and immature MHC class I before being incorporated into transporter-associated with antigen processing-1 (TAP-1)-associated peptide-loading complex. Importantly, ERO1-α regulates the redox state as well as cell surface expression of MHC class I, leading to alteration of susceptibility by CD8+ T cell. Similarly, the ERO1-α expression within cancer cells was associated with the expression level of MHC class I in colon cancer tissues. Thus, the cancer-associated ERO1-α regulates the expression of MHC class I molecule via oxidative protein folding within hypoxic tumor microenvironment.
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