The role of polycomb protein expression and application for epigenetic therapy in cholangiocarcinoma.
Project/Area Number |
24592033
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Digestive surgery
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Research Institution | Kumamoto University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
BEPPU Toru 熊本大学, 医学部附属病院, 特任教授 (70301372)
OKABE Hirohisa 熊本大学, 医学部附属病院, 特任助教 (40573621)
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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 |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | Enhancer / cholangiocarcinoma / epigenetics / cell cycle / apoptosis / p16INK4A / p27KIP1 / 3-deazaneplanocin A / Zeste Homolog 2 / Cholangiocarcinoma / gemcitabine / EZH2 / ポリコーム蛋白 / 胆管癌 / 細胞周期 / アポトーシス / DZNep |
Outline of Final Research Achievements |
In Intra- and extra-hepatic cholangiocarcinoma patients, EZH2 high expression was significantly correlated with the poor prognosis by using immunohistochemical analysis. In vitro analysis, knockdown of EZH2 reduced cell growth and induced G1 arrest, and induced apoptosis. Moreover, a knockdown of EZH2 increased the expression of p16INK4A and p27KIP1 in real time PCR. An EZH2 inhibitor, DZNep reduce the expression of EZH2 and demethylase H3K27, and result to reduce cell proliferation. Inhibition of EZH2 by DZNep also induced G1 arrest and induced apoptosis, and increased the expression of p16INK4A and p27KIP1 which revealed by western blotting. As conclusion, this study demonstrates that the high expression of EZH2 accelerate tumor malignancy and is related to poor prognosis in patients with cholangiocarcinoma. Pharmacological inhibition of EZH2 by DZNep can also inhibit cell proliferation. These results suggest that EZH2 is a potential therapeutic target for cholangiocarcinoma.
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Report
(4 results)
Research Products
(11 results)
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[Journal Article] EZH2 Is Associated with Malignant Behavior in Pancreatic IPMN via p27Kip1 Downregulation2014
Author(s)
Kuroki H, Hayashi H, Okabe H, Hashimoto D, Takamori H, Nakahara O, Nakagawa S, Fukushima Y, Chikamoto A, Beppu T, Hirota M, Iyama K, Baba H
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Journal Title
PLOS ONE
Volume: 9(8)
Issue: 8
Pages: e100904-e100904
DOI
Related Report
Peer Reviewed
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[Journal Article] Triple positive tumor markers predict recurrence and survival in early stage hepatocellular carcinoma2014
Author(s)
Nakagawa S, Beppu T, Okabe H, Sakamoto K, Kuroki H, Mima K, Nitta H, Imai K, Hayashi H, Sakamoto Y, Hashimoto D, Chikamoto A, Ishiko T, Watanabe M, Baba H
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Journal Title
Hepatol Res
Volume: 44(9)
Issue: 9
Pages: 964-74
DOI
Related Report
Peer Reviewed
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[Journal Article] Epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A inhibits the growth of cholangiocarcinoma cells.2014
Author(s)
Nakagawa S, Sakamoto Y, Okabe H, Hayashi H, Hashimoto D, Yokoyama N, Tokunaga R, Sakamoto K, Kuroki H, Mima K, Beppu T, Baba H.
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Journal Title
Oncology Report
Volume: 31
Issue: 2
Pages: 983-8
DOI
Related Report
Peer Reviewed
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[Journal Article] Enhancer of Zeste Homolog 2 (EZH2) Promotes Progression of Cholangiocarcinoma Cells by Regulating Cell Cycle and Apoptosis.2013
Author(s)
Nakagawa S, Okabe H, Sakamoto Y, Hayashi H, Hashimoto D, Yokoyama N, Sakamoto K, Kuroki H, Mima K, Nitta H, Imai K, Chikamoto A, Watanabe M, Beppu T, Baba H.
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Journal Title
Ann Surg Oncol
Volume: 3
Issue: S3
Pages: 667-675
DOI
Related Report
Peer Reviewed
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[Presentation] Enhancer of zeste homolog 2 (EZH2) promotes progression of cholangiocarcinoma by regulating cell cycle and apoptosis2013
Author(s)
Shigeki Nakagawa, Hirohisa Okabe, Yasuo Sakamoto, Hiromitsu Hayashi, Daisuke Hashimoto, Hideyuki Kuroki, Katsunori Imai, Hidetoshi Nitta, Akira Chikamoto, Masayuki Watanabe, Toru Beppu, Hideo Baba
Organizer
American Association of Cancer Research2013
Place of Presentation
アメリカ・ワシントン
Related Report
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