Histone demethylase regulate mammary gland dvelopment and breast cancer development

• Project/Area Number: 26893309
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: Kinki University
• Principal Investigator: OKADA Hitoshi 近畿大学, 医学部, 教授 (20280620)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: エピジェネティクス / 乳がん / エストロゲン受容体 / エストロゲン / ヒストン / エピジネティクス

Outline of Final Research Achievements

The estrogen receptor (ER) signaling pathway is the established therapeutic target of Luminal A breast cancer, thus determining the molecular basis of the ER signaling pathway is crucial for understanding the biology of breast cancer and overcoming hormone therapy resistance.
We have identified that an H3K9 histone lysine demethylase, KDM4B/JMJD2B, regulates estrogen signaling pathway by acting as a transcriptional co-activator for promoting ER-dependent cell proliferation. In addition, further cell biological, biochemical, and epigenomic analyses of human cancer cell lines and our tissue-specific Kdm4b knockout mice have uncovered the full spectrum of activities of KDM4B in regulating critical oncogenic signaling pathways and mammary gland development. We thus propose that KDM4B signaling pathway is a potential target for cancer treatment.

Research Products

• [Int'l Joint Research] Davidoff AM, Harris AL他/St. Jude Children’s Research Hospital/University of Oxford(米国、英国、ギリシャ、オランダ)
• [Journal Article] Deletion of JMJD2B in neurons leads to defective spine maturation, hyperactive behavior, and memory deficits in mouse. (2016)
  • Author(s): Fujiwara, K., Fujita, Y., Kasai, A., Onaka, Y., Hashimoto, H., Okada, H. and Yamashita, T.
  • Journal Title: Transl. Psychiatry Volume: 6 Issue: 3 Pages: e766-e766
  • DOI: 10.1038/tp.2016.31
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Loss of Survivin in Intestinal Epithelial Progenitor Cells Leads to Mitotic Catastrophe and Breakdown of Gut Immune Homeostasis (2016)
  • Author(s): Eva Martini , Nadine Wittkopf , Claudia Günther , Moritz Leppkes , Hitoshi Okada , Alastair J. Watson , Eva Podstawa , Ingo Backert , Kerstin Amann , Markus F. Neurath , Christoph Becker
  • Journal Title: Cell reports Volume: 14 Issue: 5 Pages: 1062-1073
  • DOI: 10.1016/j.celrep.2016.01.010
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Role of Histone Demethylase KDM4B in Myc Signaling in Neuroblastoma (2015)
  • Author(s): Jun Yang, Alaa M. AlTahan, Dongli Hu, Yingdi Wang, Pei-Hsin Cheng, Christopher L. Morton, Chunxu Qu, Amit C. Nathwani, Jason M. Shohet, Theodore Fotsis, Jan Koster, Rogier Versteeg, Hitoshi Okada, Adrian L. Harris and Andrew M. Davidoff
  • Journal Title: Journal of the National Cancer Institute Volume: 107 Issue: 6
  • DOI: 10.1093/jnci/djv080
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Histone lysine demethylase and human diseases (2014)
  • Author(s): Okada H
  • Journal Title: Acta Med Kinki Univ. Volume: 39 Pages: 1-10
  • Open Access
• [Presentation] ヒストン脱メチルか酵素UTXによる脂肪細胞分化メカニズムの解明 (2015)
  • Author(s): 太田一成、Kit I Tong、後藤幸一郎、古室顕義、岡田斉
  • Organizer: 第38回日本分子生物学会、第88回日本生化学学会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2015-12-03
• [Presentation] ヒストン脱メチル化酵素による乳腺発達制御 (2015)
  • Author(s): 岡田斉
  • Organizer: 第38回日本分子生物学会、第88回日本生化学学会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2015-12-01
• [Presentation] Histone demethylase, KDM4B/JMJD2B, constitutes a key component of oncogenic signaling pathways (2015)
  • Author(s): Hitoshi Okada
  • Organizer: 第74回日本癌学会 コアシンポジウム「遺伝子プログラム異常による発がん機構と治療標的としての活用」
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-10-08
• [Presentation] ヒストン脱メチル化酵素KDM4B(JMJD2B)欠損による肥満誘導 (2014)
  • Author(s): 岡田 斉
  • Organizer: 日本生化学会
  • Place of Presentation: 京都国際会館
  • Year and Date: 2014-10-16