Molecular mechanism of transcriptional regulation by NFATc in tumor endothelial cells

• Project/Area Number: 24700969
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Kyorin University (2013); The University of Tokyo (2012)
• Principal Investigator: SUEHIRO JUNICHI 杏林大学, 医学部, 助教 (80572601)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); 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)
• Keywords: 血管内皮細胞 / 腫瘍血管新生 / ＶＥＧＦ / ＮＦＡＴｃ / NFATc / タンパク質相互作用 / in vivo発現解析 / ＣｈＩＰ－ｓｅｑ

Research Abstract

To elucidate molecular mechanism of transcriptional activation by NFATc, I performed global analysis of target genes using microarray and ChIP-seq and examined beta-galactosidase activities in hprt locus-target in EGR3 promoter-lacZ transgenic mice. CXCR7 and RND1 were first identified as NFATc targets and contributed to VEGF-mediated angiogenesis. NFAT-mediated EGR3 promoter activities in vivo were upregulated by inflammatory stimuli in various types of endothelial cells.

Research Products

• [Journal Article] The Calcineurin-NFAT-Angiopoietin-2 Signaling Axis in Lung Endothelium Is Critical for the Establishment of Lung Metastases (2013)
  • Author(s): Minami T, Jiang S, Schadler K, Suehiro JI, Osawa T, Oike Y, Miura M, Naito M, Kodama T, Ryeom S
  • Journal Title: Cell Reports Volume: Aug 14. pii:S2211-1247(13) Issue: 4 Pages: 383-5
  • DOI: 10.1016/j.celrep.2013.07.021
  • Peer Reviewed
• [Journal Article] Inhibition of histone demethylase JMJD1A improves anti-angiogenic therapy and reduces tumor associated macrophages (2013)
  • Author(s): Shimamura T, Wang F, Suehiro J, Kanki Y, Wada Y, Yuasa Y, Aburatani H, Miyano S, Minami T, Kodama T, Shibuya M
  • Journal Title: Cancer Res Volume: 73 Issue: 10 Pages: 3019-3028
  • DOI: 10.1158/0008-5472.can-12-3231
  • Peer Reviewed
• [Journal Article] The COUP-TFII variant lacking a DNA-binding domain inhibits the activation of the Cyp7a1 promoter through physical interaction with COUP-TFII (2013)
  • Author(s): Yamazaki T, Suehiro J, Miyazaki H, Minami T, Kodama T, Miyazono K, Watabe T.
  • Journal Title: Biochemical Journal Volume: 452 Issue: 2 Pages: 345-357
  • DOI: 10.1042/bj20121200
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Dynamic change of chromatin conformation in response to hypoxia enhances the expression of GLUT3 (SLC2A3) by cooperative interaction of hypoxia-inducible factor 1 and KDM3A. (2012)
  • Author(s): Mimura I
  • Journal Title: Mol Cell Biol. Volume: Aug;32(15) Issue: 15 Pages: 3018-3032
  • DOI: 10.1128/mcb.06643-11
  • Peer Reviewed
• [Presentation] 血管内皮細胞増殖因子を介した血管ネットワーク形成におけるアミノ酸トランスポーターLAT1の役割 (2013)
  • Author(s): 末弘淳一、木村徹、櫻井裕之
  • Organizer: 第129回日本薬理学会関東部会
  • Place of Presentation: 東京
  • Year and Date: 2013-10-19
• [Presentation] LAT1阻害は血管内皮細胞増殖を抑制する (2013)
  • Author(s): 末弘淳一、櫻井裕之
  • Organizer: 生理研研究会『上皮膜輸送の多層的コントロールによる生体の恒常性維持機構 』
  • Place of Presentation: 愛知
  • Year and Date: 2013-08-26
• [Presentation] 血管内皮細胞におけるLAT1選択的阻害薬JPH203の薬理学的検討 (2013)
  • Author(s): 末弘淳一、櫻井裕之
  • Organizer: 第128回日本薬理学会関東部会
  • Place of Presentation: 東京
  • Year and Date: 2013-07-14
• [Presentation] The calcineurin/NFATc signaling axis regulates VEGF-mediated angiogenesis and vascular integrity (2013)
  • Author(s): 末弘淳一、神吉康晴、油谷浩幸、浜窪隆雄、児玉龍彦、南敬
  • Organizer: 第1回生活習慣病の分子細胞病態学研究会
  • Place of Presentation: 東京
  • Year and Date: 2013-03-23
• [Presentation] Temporal-spatial analysis of Egr-3 promoter activities in hprt locus target-in transgenic mice (2012)
  • Author(s): Jun-ichi Suehiro, Takashi Minami
  • Organizer: 第20回血管生物医学会学術集会
  • Place of Presentation: 徳島
  • Year and Date: 2012-12-07
• [Presentation] calcineurin- NFATcシグナルがVEGFを介した血管新生と病的な内皮細胞の表現型に寄与する (2012)
  • Author(s): 末弘淳一, 南敬
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-20
• [Presentation] Genome-wide approaches reveal functional VEGF-NFATc-mediated RND1 induction is necessary for endothelial barrier potential (2012)
  • Author(s): Jun-ichi Suehiro, Yasuharu Kanki, Takashi Minami
  • Organizer: IVBM2012
  • Place of Presentation: Wiesbaden
  • Year and Date: 2012-06-03
• [Presentation] 血管内皮細胞におけるLAT1選択的阻害薬JPH203の薬理学的検討.
  • Author(s): 末弘 淳一、櫻井 裕之
  • Organizer: 第128回日本薬理学会関東部会
  • Place of Presentation: 東京
• [Presentation] LAT1 阻害は血管内皮細胞増殖を抑制する
  • Author(s): 末弘 淳一、櫻井 裕之
  • Organizer: 生理研研究会「上皮膜輸送の多層的コントロールによる生体の恒常性維持機構」
  • Place of Presentation: 愛知
• [Presentation] 血管内皮細胞増殖因子を介した血管ネットワーク形成におけるアミノ酸トランスポーターLAT1の役割
  • Author(s): 末弘 淳一、木村 徹、櫻井 裕之
  • Organizer: 第129回日本薬理学会関東部会
  • Place of Presentation: 東京
• [Presentation] Genome-wide approaches reveal functional VEGF-NFATc-mediated RND1 induction is necessary for endothelial barrier potential．
  • Author(s): Jun-ichi Suehiro, Yasuharu Kanki, Takashi Minami
  • Organizer: IVBM2012
  • Place of Presentation: Wiesbaden(Germany)
• [Presentation] calcineurin-NFATcシグナルがVEGFを介した血管新生と病的な内皮細胞の表現型に寄与する．
  • Author(s): 末弘 淳一, 南 敬
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] Temporal-spatial analysis of Egr-3 promoter activities in hprt locus target-in transgenic mice.
  • Author(s): Jun-ichi Suehiro, Takashi Minami.
  • Organizer: 第20回血管生物医学会学術集会
  • Place of Presentation: 徳島
• [Presentation] The calcineurin/NFATc signaling axis regulates VEGF-mediated angiogenesis and vascular integrity.
  • Author(s): 末弘 淳一、神吉 康晴、油谷 浩幸、浜窪 隆雄、児玉 龍彦、南 敬
  • Organizer: 第1回生活習慣病の分子細胞病態学研究会
  • Place of Presentation: 東京
• [Remarks]
  • URL: http://www.vb.rcast.u-tokyo.ac.jp/
• [Remarks]
  • URL: http://www.kyorin-u.ac.jp/univ/user/medicine/pharmaco/
• [Remarks] 東京大学先端科学技術研究センター血管生物学分野
  • URL: http://www.vb.rcast.u-tokyo.ac.jp/
• [Remarks] 杏林大学医学部薬理学教室
  • URL: http://www.kyorin-u.ac.jp/univ/user/medicine/pharmaco/
• [Remarks] 東京大学先端科学技術研究センター血管生物学分野
  • URL: http://www.vb.rcast.u-tokyo.ac.jp/
• [Remarks] 杏林大学医学部：教員紹介 末弘 淳一
  • URL: http://www.kyorin-u.ac.jp/univ/faculty/medicine/education/staff/detail/?id=med50010
• [Patent(Industrial Property Rights)] 血管内皮細胞の活性化に起因する疾患の治療又は予防剤 (2013)
  • Inventor(s): 南敬、末弘淳一、神吉康晴
  • Industrial Property Rights Holder: 国立大学法人東京大学(504137912)
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-01-28
• [Patent(Industrial Property Rights)] 血管内皮細胞の活性化に起因する疾患の治療又は予防剤 (2013)
  • Inventor(s): 南敬、末弘淳一、神吉康晴
  • Industrial Property Rights Holder: 国立大学法人東京大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-013530
  • Filing Date: 2013-01-28