Development of novel cancer therapy through the targeting bromodomain protein

• Project/Area Number: 23790126
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Drug development chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: YAMAGUCHI Kiyoshi 東京大学, 医科学研究所, 助教 (50466843)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ゲノム創薬 / 大腸がん / 分子標的治療 / ヒストン修飾 / 発現制御 / ゲノム

Research Abstract

Accumulation of BRD8 is frequently observed in colorectal cancer cells. We found that this accumulation resulted from deregulation of ubiquitin-proteasome system. Genome-wide gene expression profiling of BRD8-knocked down cells unveiled association of BRD8 with cancer progression. BRD8 may be an attractive therapeutic target for colorectal cancer.

Research Products

• [Journal Article] Wnt3a stimulates maturation of impaired neutrophils developed from severe congenital neutropenia-derived pluipotent stem cells with heterozygous ELANE mutation. (2013)
  • Author(s): Hiramoto T
  • Journal Title: Proc Natl Acad Sci USA Volume: 110 Issue: 8 Pages: 3023-3028
  • DOI: 10.1073/pnas.1217039110
  • Peer Reviewed
• [Journal Article] MRG-binding protein contributes to colorectal cancer development. (2011)
  • Author(s): Yamaguchi K, Sakai M, Kim J, Tsunesumi S, Fujii T, Ikenoue T, Yamada Y, Akiyama Y, Muto Y, Yamaguchi R, Miyano S, Nakamura Y, Furukawa Y.
  • Journal Title: Cancer Sci. Volume: 102(8) Pages: 1486-1492
  • NAID: 10030242078
  • Peer Reviewed
• [Journal Article] Smyd3 is required for the development of cardiac and skeletal muscle in zebrafish. (2011)
  • Author(s): Fujii T, Tsunesumi S, Yamaguchi K, Watanabe S, Furukawa Y.
  • Journal Title: PLoS One. Volume: 6(8) Issue: 8 Pages: e23491-e23491
  • DOI: 10.1371/journal.pone.0023491
  • Peer Reviewed
• [Journal Article] MRG-binding protein contributes to colorectal cancer development (2011)
  • Author(s): Yamaguchi K, Sakai M, Kim J, Tsunesumi S, Fujii T, Ikenoue T, Yamada Y, Akiyama Y, Muto Y, Yamaguchi R, Miyano S, Nakamura Y, Furukawa Y
  • Journal Title: Cancer Sci Volume: 102 Pages: 1486-1492
  • NAID: 10030242078
  • Peer Reviewed
• [Journal Article] Smyd3 is required for the development of cardiac and skeletal muscle in zebrafish (2011)
  • Author(s): Fujii T, Tsunesumi S, Yamaguchi K, Watanabe S, Furukawa Y
  • Journal Title: PLoS One Volume: 6
  • Peer Reviewed
• [Presentation] DSCC1 is a novel biomarker for chemo-resistant colorectal cancer (2013)
  • Author(s): Kiyoshi Yamaguchi, Rui Yamaguchi, Masaru Shinozaki, Giichiro Tsurita, Keisuke Hata, Seiya Imoto, Satoru Miyano, Yusuke Nakamura, Yoichi Furukawa.
  • Organizer: 9th AACR-JCA Joint Conference
  • Place of Presentation: Hyatt Regency Maui (Maui HI, USA)
  • Year and Date: 2013-02-21
• [Presentation] DSCC1 is a novel biomarker for chemo-resistant colorectal cancer. (2013)
  • Author(s): Kiyoshi Yamaguchi, Rui Yamaguchi, Masaru Shinozaki, Giichiro Tsurita, Keisuke Hata, Seiya Imoto, Satoru Miyano, Yusuke Nakamura, Yoichi Furukawa
  • Organizer: 9th AACR-JCA Joint Conference
  • Place of Presentation: Maui HI, USA
• [Presentation] DSCC1 promotes survival of colorectal cancer cells through the induction of BCL2 expression (2012)
  • Author(s): Kiyoshi Yamaguchi, Rui Yamaguchi, Masaru Shinozaki, Giichiro Tsurita, Keisuke Hata, Seiya Imoto, Satoru Miyano, Yusuke Nakamura, Yoichi Furukawa.
  • Organizer: 8th International Symposium on Cancer Research and Therapy
  • Place of Presentation: 東京会館(東京)
  • Year and Date: 2012-11-09
• [Presentation] Identifying the target of histone methyltransferase SMYD3 in colorectal cancer cells (2012)
  • Author(s): 山口貴世志,池上恒雄,宮野悟,中村祐輔,古川洋一
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌(札幌)
  • Year and Date: 2012-09-19
• [Presentation] Identifying the target of histone methyltransferase SMYD3 in colorectal cancer cells. (2012)
  • Author(s): 山口貴世志, 池上恒雄, 宮野悟, 中村祐輔, 古川洋一
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌（札幌）
• [Presentation] DSCC1 promotes survival of colorectal cancer cells through the induction of BCL2 expression. (2012)
  • Author(s): Kiyoshi Yamaguchi, Rui Yamaguchi, Masaru Shinozaki, Giichiro Tsurita, Keisuke Hata, Seiya Imoto, Satoru Miyano, Yusuke Nakamura, Yoichi Furukawa
  • Organizer: 8th International Symposium on Cancer Research and Therapy
  • Place of Presentation: 東京会館（東京）
• [Presentation] Defective in sister chromatid cohesion 1 homolog (DSCC1), a novel target of E2F1 is overexpressed in colorectal cancer (2011)
  • Author(s): 山口貴世志,藤井智明,池上恒雄,中村祐輔,古川洋一
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2011-10-03
• [Presentation] MRGBP (C20orf20) contributes to development of colorectal cancer (2011)
  • Author(s): Kiyoshi Yamaguchi, Michihiro Sakai, JooHun Kim, Yoshinao Yamada, Yoshiyuki Akiyama, Yusuke Nakamura, and Yoichi Furukawa.
  • Organizer: American Association for Cancer Research102th Annual Meeting
  • Place of Presentation: Orange County Convention Center (Orlando FL, USA)
  • Year and Date: 2011-04-02
• [Presentation] Defective in sister chromatid cohesion 1 homolog (DSCC1), a novel target of E2F1 is overexpressed in colorectal cancer (2011)
  • Author(s): 山口貴世志, 藤井智明, 池上恒雄, 中村祐輔, 古川洋一
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋