| Project/Area Number |
23591009
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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 |
Gastroenterology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
KOGURE Hirofumi 東京大学, 医学部附属病院, 助教 (60568921)
SASAKI Takashi 東京大学, 医学部附属病院, 助教 (10569106)
YAMAMOTO Natsuyo 東京大学, 医学部附属病院, 助教 (40599578)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 膵がん / ヒストン修飾 / エピジェネテイクス / 膵癌 |
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| Research Abstract |
Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease where virtually all tumors harbor mutations in KRAS and other tumor suppressor genes. Though recent studies provide evidence that epigenetic changes, as well as genetic mutations, are involved in the initiation and progression of cancer, the impact of epigenetic alteration in PDAC is yet to be determined.Here we focused on the histone H3 Lys 27 (H3K27) demethylase KDM6B. KDM6B is a putative tumor suppressor and previous reports have shown that KDM6B is upregulated under oncogenic KRAS mutations and activates tumor suppressor p16/CDKN2A, thus inducing oncogene-induced senescence (OIS) in premalignant lesions. In this work, we identified a novel tumor suppressive mechanism by KDM6B, distinct from the KRAS-KDM6B-p16 mediated induction of OIS. We provide evidence that loss of KDM6B-C/EBP axis enhances tumorigenesis in PDAC cells.
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