2012 Fiscal Year Final Research Report
EB virus-associated gastric carcinoma. Molecular mechanisms of DNA hypermethylation and strategy for gastric cancer therapy.
| Project/Area Number |
20249022
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
UOZAKI Hiroshi 東京大学, 大学院・医学系研究科, 講師(H23より准教授) (10296246)
SAKATANI Takashi 東京大学, 大学院・医学系研究科, 助教 (50431903)
HINO Rumi 東京大学, 大学院・医学系研究科, 助教 (60451770)
USHIKU Tetsuo 東京大学, 医学部附属病院, 助教 (60376415)
MORIKAWA Teppei 東京大学, 医学部附属病院, 助教 (80451772)
KIKUCHI Yoshinao 東京大学, 医学部附属病院, 助教 (90512260)
NAKAYA Takeo 東京大学, 大学院・医学系研究科, 特任助教 (80512277)
SHINOZAKI Aya 東京大学, 大学院・医学系研究科, 助教 (60581824)
KUNITA Akiko 東京大学, 大学院・医学系研究科, 助教 (50608768)
MATSUSAKA Keisuke 東京大学, 医学部附属病院, 助教 (40610150)
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| Project Period (FY) |
2008 – 2012
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| Keywords | EBウイルス関連胃癌 / EBウイルス / 胃癌 / エピジェネティクス / LMP2A / SP細胞 / トランスジェニックマウス / マイクロRNA |
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| Research Abstract |
Methylation array analyses demonstrated that EBV-associated GC showed genome-wide hypermethylation at CpG sites of promoter regions. We succeeded in reproducing this genome-wide methylation by EBV infection of the gastric cancer cell line, MKN7, which serves as an important experimental system to investigate the molecular mechanisms. We demonstrated that a viral latent protein, LMP2A, partially contributed to the DNA hypermethylation. A possible virus-reactivating therapy was evaluated with inhibitors of DNA methylation and proteosome.
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[Journal Article] ARID1Aexpression loss in gastric cancer: pathway-dependent roles with and without Epstein-Barr virus infection and microsatellite instability2012
Author(s)
Abe H, Maeda D, Hino R, Otake Y, Isogai M, Ushiku AS, Matsusaka K,Kunita A, Ushiku T, Uozaki H,Tateishi Y, Hishima T, Iwasaki Y, Ishikawa S, Fukayama M
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Journal Title
Virchows Archiv
Volume: Vol.461
Pages: 367-77
DOI
Peer Reviewed
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[Journal Article] SOX9 expression and its methylation status in gastric cancer2012
Author(s)
Sun M, Uozaki H, Hino R, Kunita A, Shinozaki A, Ushiku T, Hibiya T,Takeshita K, Isogai M, Takada K,Fukayama M
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Journal Title
Virchows Archiv
Volume: Vol.460
Pages: 271-279
DOI
Peer Reviewed
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[Journal Article] Classification of Epstein-Barr virus positive gastric cancers by definition of DNAmethylation Epigenotypes2011
Author(s)
Matsusaka K, Kaneda A, Nagae G, Ushiku T, Kikuchi Y, Hino R, Uozaki H,Seto Y, Takada K, Aburatani H, Fukayama M
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Journal Title
Cancer Research
Volume: Vol.71
Pages: 7187-97
DOI
Peer Reviewed
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[Journal Article] Activation ofDNA methyltransferase 1 by EBV Latent Membrane Protein 2A Leads to Promoter Hypermethylation of PTEN Gene in Gastric Carcinoma2009
Author(s)
Hino R, Uozaki H, Murakami N, Ushiku T, Shinozaki A, Ishikawa S,Morikawa T, Nakaya T, Sakatani T,Takada K, Fukayama M
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Journal Title
Cancer Research
Volume: Vol.69
Pages: 2766-277 4
DOI
Peer Reviewed
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[Journal Article] Bortezomib-induced enzyme-targeted radiation therapy in herpesvirus-associated tumors2008
Author(s)
Fu DX, Tanhehco Y, Chen J, Foss CA, Fox JJ, Chong JM, Hobbs RF,Fukayama M, Sgouros G, Kowalski J, Pomper MG, Ambinder RF
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Journal Title
Nature Medicine
Volume: Vol.14
Pages: 1118-1122
DOI
Peer Reviewed
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[Book] Gastric Cancer2010
Author(s)
Fukayama M, Shinozaki A, Hino R
Total Pages
38-50
Publisher
Wolters Kluwer/ Lippincott Williams& Wilkins, Advances in SurgicalPathology
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