An investigation of histone modifications that modulate malignant properties of pancreatic cancer.
| Project/Area Number |
24591009
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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) |
TATEISHI Keisuke 東京大学, 医学部附属病院・消化器内科, 講師 (20396948)
伊地知 秀明 東京大学, 医学部附属病院, 講師 (70463841)
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| Co-Investigator(Renkei-kenkyūsha) |
IJICHI Hideaki 東京大学, 医学部附属病院・消化器内科/病態栄養治療部, 講師 (70463841)
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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 |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 膵癌 / ヒストン修飾 / エピジェネティクス |
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| Outline of Final Research Achievements |
In this study, we have identified a novel KDM6B-CEBPA axis and revealed its tumor-suppressive role in pancreatic ductal adenocarcinoma (PDAC). KDM6B is a histone demethylase for H3K27me3, a repressive chromatin mark. We found that KDM6B was highly expressed in pancreatic precancerous lesions PanINs, and that the expression of KDM6B decreased as the malignant grade progressed. Notably, knockdown of KDM6B in PDAC cells enhanced aggressiveness, as shown by increased peritoneal dissemination and liver metastasis in orthotopic transplantation model using nude mice. Microarray and chromatin immunoprecipitation analysis implicated CEBPA for aggressiveness induced by KDM6B knockdown. Indeed, CEBPA knockdown recapitulated the phenotypic change of PDAC cells after KDM6B knockdown. Moreover, similar expression patterns of KDM6B and CEBPA in PDAC emphasized their functional correlation. Together, our results propose a significant role for the KDM6B-CEBPA axis in the PDAC phenotype.
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Report
(4 results)
Research Products
(3 results)
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[Journal Article] Loss of histone demethylase KDM6B enhances aggressiveness of pancreatic cancer through downregulation of C/EBPα.2014
Author(s)
Yamamoto K, Tateishi K, Kudo Y, Sato T, Yamamoto S, Miyabayashi K, Asaoka Y, Ijichi H, Hirata Y, Otsuka M, Nakai Y, Isayama H, Ikenoue T, Kurokawa M, Fukayama M, Kokudo N, Omata M and Koike K.
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Journal Title
Carcinogenesis
Volume: 35
Issue: 11
Pages: 2404-14
DOI
Related Report
Peer Reviewed / Open Access
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