2017 Fiscal Year Final Research Report
Role of oxidative stress response in pancreatic diseases and therapeutic application
| Project/Area Number |
15H04804
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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 |
Gastroenterology
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
濱田 晋 東北大学, 医学系研究科, 助教 (20451560)
田口 恵子 東北大学, 医学系研究科, 講師 (20466527)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | 酸化ストレス |
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| Outline of Final Research Achievements |
We assessed the effect of continuous Nrf2 activation due to the pancreas-specific deletion of Keap1 in a mouse model of pancreatic cancer. Pancreas-specific expression of mutant Kras and p53 or Kras alone with conditional knockout of Keap1 resulted in poor weight gain after birth, leading to early death due to loss of pancreatic parenchyma. Additional introduction of Nrf2+/- or Nrf2-/- background rescued this phenotype, suggesting dependence to Nrf2. We observed no cancer promoting effect in KPC::Keap1 CKO::Nrf2+/- mice. Pancreatic cancer cell lines derived from these mice showed increased expression of Nrf2 target genes as well as decreased expression of cytokeratin family genes, indicating possible reprogramming of cellular phenotype.
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| Free Research Field |
膵臓病学
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