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Functional analysis of a novel bromodomain protein in cancer cells

Research Project

Project/Area Number 26860206
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pathological medical chemistry
Research InstitutionThe University of Tokyo

Principal Investigator

Yamaguchi Kiyoshi  東京大学, 医科学研究所, 特任講師 (50466843)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords分子標的治療 / 大腸がん / 遺伝子発現 / エピジェネティクス / ゲノム
Outline of Final Research Achievements

Bromodomain containing 8 (BRD8) is frequently accumulated in colorectal cancer. Although BRD8 has been considered to alter gene expression through epigenetic modification, genes regulated by BRD8 remain largely unknown. In this study, we analyzed the data of a transcriptome, ChIP-seq, and ChIA-PET, and identified a total of 49 genes that are directly regulated by BRD8. Interestingly, the list includes a gene associated with the regulation of an oncogenic signaling pathway. Consistently, knockdown of BRD8 reduced the expression of downstream gene, leading to change in the activity of the signaling pathway. Since BRD8 is a component in TRRAP/TIP60-histone acetyltransferase complex, our data may help for the development of novel strategies to treat human cancer through targeting the acetyltransferase complex.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (23 results)

All 2016 2015 2014

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (13 results) (of which Int'l Joint Research: 2 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Genetic alterations in Japanese extrahepatic biliary tract cancer.2016

    • Author(s)
      Noguchi R, Yamaguchi K, Ikenoue T, Terakado Y, Ohta Y, Yamashita N, Kainuma O, Yokoi S, Maru Y, Nagase H, Furukawa Y
    • Journal Title

      Oncol Lett

      Volume: 印刷中

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel mouse model of intrahepatic cholangiocarcinoma induced by liver-specific Kras activation and Pten deletion2016

    • Author(s)
      Ikenoue T, Terakado Y, Nakagawa H, Hikiba Y, Fujii T, Matsubara D, Noguchi R, Zhu C, Yamamoto K, Kudo Y, Asaoka Y, Yamaguchi K, Ijichi H, Tateishi K, Fukushima N, Maeda S, Koike K, Furukawa Y
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 23899-23899

    • DOI

      10.1038/srep23899

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Detection of APC mosaicism by next-generation sequencing in an FAP patient.2015

    • Author(s)
      Yamaguchi K, Komura M, Yamaguchi R, Imoto S, Shimizu E, Kasuya S, Shibuya T, Hatakeyama S, Takahashi N, Ikenoue T, Hata K, Tsurita G, Shinozaki M, Suzuki Y, Sugano S, Miyano S, Furukawa Y
    • Journal Title

      J Hum Genet

      Volume: 60(5) Issue: 5 Pages: 227-231

    • DOI

      10.1038/jhg.2015.14

    • NAID

      40020462565

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Molecular profiles of high-grade and low-grade pseudomyxoma peritonei.2015

    • Author(s)
      Noguchi R, Yano H, Gohda Y, Suda R, Igari T, Ohta Y, Yamashita N, Yamaguchi K, Terakado Y, Ikenoue T, Furukawa Y
    • Journal Title

      Cancer Med

      Volume: 4(12) Issue: 12 Pages: 1809-1816

    • DOI

      10.1002/cam4.542

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A novel APC mosaicism in a patient with familial adenomatous polyposis.2015

    • Author(s)
      Moriya Iwaizumi, Ken Sugimoto, et al.
    • Journal Title

      Hum Genome Var

      Volume: 10 Issue: 1 Pages: 15057-15057

    • DOI

      10.1038/hgv.2015.57

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Disruption of Wnt/β-catenin signaling and telomeric shortening are inextricable consequences of tankyrase inhibition in human cells.2015

    • Author(s)
      Kulak O, Chen H, Holohan B, Wu X, He H, Borek D, Otwinowski Z, Yamaguchi K, Garofalo LA, Ma Z, Wright W, Chen C, Shay JW, Zhang X, Lum L
    • Journal Title

      Mol Cell Biol

      Volume: 35(14) Issue: 14 Pages: 2425-2435

    • DOI

      10.1128/mcb.00392-15

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Identification of therapeutic small-molecule leads in cultured cells using multiplexed pathway reporter readouts. Chemical Biology--Methods and Protocols2015

    • Author(s)
      Kulak O, Yamaguchi K, Lum L
    • Journal Title

      Methods Mol Biol

      Volume: 1263 Pages: 3-14

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Attenuated familial adenomatous polyposis with desmoids by an APC mutation2015

    • Author(s)
      Ikenoue T, Yamaguchi K, Komura M, Imoto S, Yamaguchi R, Shimizu E, Kasuya S, Shibuya T, Hatakeyama S, Miyano S, Furukawa Y
    • Journal Title

      Hum Genome Variation

      Volume: 2 Pages: 15011-15011

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 全ゲノム解析により同定された腺腫性大腸ポリポーシス患者のAPC遺伝子転写調節領域の欠失2015

    • Author(s)
      山口貴世志, 上村光弘, 清水英悟, 長山聡, 山口類, 井元清哉, 渋谷哲朗, 池上恒雄, 宮野悟, 古川洋一
    • Organizer
      日本人類遺伝学会 第60回大会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2015-10-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] Efficacy of target enrichment-based sequencing for identifying genetic alterations in familial colorectal cancer.2015

    • Author(s)
      山口貴世志, 陶弘, 倉地清隆, 前川真人, 岩泉守哉, 中村利夫, 井元清哉, 山口類, 上村光弘, 宮野悟, 椙村春彦, 古川洋一
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] Next-generation sequencing detects a mosaic APC mutation present at low allele frequencies in an FAP patient.2015

    • Author(s)
      Kiyoshi Yamaguchi, Mitsuhiro Komura, Rui Yamaguchi, Seiya Imoto, Eigo Shimizu, Shinichi Kasuya, Tetsuo Shibuya, Seira Hatakeyama, Norihiko Takahashi, Tsuneo Ikenoue, Keisuke Hata, Giichiro Tsurita, Masaru Shinozaki, Yutaka Suzuki, Sumio Sugano, Satoru Miyano, Yoichi Furukawa
    • Organizer
      The Clinical Genome Conference
    • Place of Presentation
      San Francisco CA (USA)
    • Year and Date
      2015-06-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Next-generation sequencing as a potential tool in the diagnostics of APC mosaicism in FAP patient.2015

    • Author(s)
      Kiyoshi Yamaguchi, Mitsuhiro Komura, Rui Yamaguchi, Seiya Imoto, Eigo Shimizu, Shinichi Kasuya, Tetsuo Shibuya, Seira Hatakeyama, Norihiko Takahashi, Tsuneo Ikenoue, Keisuke Hata, Giichiro Tsurita, Masaru Shinozaki, Yutaka Suzuki, Sumio Sugano, Satoru Miyano, Yoichi Furukawa
    • Organizer
      American Association for Cancer Research 106th Annual Meeting
    • Place of Presentation
      Philadelphia PA (USA)
    • Year and Date
      2015-04-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Bromodomain Protein BRD8 is a novel therapeutic target for colorectal cancer2014

    • Author(s)
      Kiyoshi Yamaguchi, Masashi Miura, Chi Zhu, Tsuneo Ikenoue, Satoru Nagatoishi, Kouhei Tsumoto, Yoichi Furukawa
    • Organizer
      9th International Symposium on Cancer Research and Therapy
    • Place of Presentation
      東京
    • Year and Date
      2014-10-31 – 2014-11-01
    • Related Report
      2014 Research-status Report
  • [Presentation] Identification of genetic alterations in biliary tract cancer using multiplex PCR for cancer associated genes2014

    • Author(s)
      Rei Noguchi, Kiyoshi Yamaguchi, Yasunori Ohta, Tsuneo Ikenoue, Yoichi Furukawa
    • Organizer
      9th International Symposium on Cancer Research and Therapy
    • Place of Presentation
      東京
    • Year and Date
      2014-10-31 – 2014-11-01
    • Related Report
      2014 Research-status Report
  • [Presentation] Establishment of a novel mouse model of intrahepatic cholangiocarcinoma using liver-specific Kras activation and Pten deletion2014

    • Author(s)
      Tsuneo Ikenoue, Yumi Terakado, Kiyoshi Yamaguchi, Yoichi Furukawa
    • Organizer
      9th International Symposium on Cancer Research and Therapy
    • Place of Presentation
      東京
    • Year and Date
      2014-10-31 – 2014-11-01
    • Related Report
      2014 Research-status Report
  • [Presentation] Search for pathogenic variants in familial colorectal cancer using a next generation sequencer2014

    • Author(s)
      山口貴世志, 上村光弘, 清水英悟, 粕谷慎一, 山口類, 渋谷哲朗, 井元清哉, 長山聡, 高橋則彦, 池上恒雄, 菅野純夫, 鈴木穣, 宮野悟, 古川洋一
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Genetic analysis of cancer associated genes in Japanese biliary tract cancer using next generation sequencer2014

    • Author(s)
      野口玲, 山口貴世志, 荒川茉莉子, 太田泰徳, 池上恒雄, 古川洋一
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] The interferon-induced protein family is down-regulated through the canonical WNT-signaling pathway2014

    • Author(s)
      大杉友之, 山口貴世志, 朱赤, 黄雨晴, 池上恒雄, 古川洋一
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Genetic analysis for hereditary tumors by exome sequencing2014

    • Author(s)
      荒川茉莉子, 野口玲, 山口貴世志, 粕谷慎一, 山口類, 井元清哉, 宮野悟, 池上恒雄, 古川洋一
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] A novel mouse model of intrahepatic cholangiocarcinoma induced by liver-specific Kras activation and Pten deletion2014

    • Author(s)
      寺門侑美, 池上恒雄, 山口貴世志, 浅岡良成, 伊地知秀明, 立石敬介, 小池和彦, 古川洋一
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] リンチ症候群を強く疑わせる家族歴を持つ、同時多発大腸がんの症例2014

    • Author(s)
      野口玲, 山口貴世志, 矢野秀朗, 合田良政, 須田竜一郎, 池上恒雄, 古川洋一
    • Organizer
      第20回家族性腫瘍学会 学術集会
    • Place of Presentation
      福島
    • Year and Date
      2014-06-13 – 2014-06-14
    • Related Report
      2014 Research-status Report
  • [Book] 臨床病理レビュー コンパニオン診断の進展2015

    • Author(s)
      山口貴世志, 古川洋一
    • Total Pages
      89
    • Publisher
      克誠堂出版
    • Related Report
      2015 Annual Research Report
  • [Patent(Industrial Property Rights)] 転写因子を調節する上流のシグナル伝達経路および転写因子の活性を制御する分子および物質のスクリーニング方法2015

    • Inventor(s)
      古川 洋一, 山口 貴世志
    • Industrial Property Rights Holder
      国立大学法人東京大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-027182
    • Filing Date
      2015-02-16
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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