Pyrrole-imidazole polyamide targeted to break fusion sites in TMPRSS2 and ERG gene fusion represses prostate tumor growth

Authors

  • Daisuke Obinata,

    1. Department of Urology, Nihon University School of Medicine, Tokyo, Japan
    2. Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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    • These authors contribute equally to this work.
  • Akiko Ito,

    1. Department of Urology, Nihon University School of Medicine, Tokyo, Japan
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    • These authors contribute equally to this work.
  • Kyoko Fujiwara,

    1. Division of General Medicine, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
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    • These authors contribute equally to this work.
  • Ken-Ichi Takayama,

    1. Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
    2. Department of Geriatric Medicine, The University of Tokyo, Tokyo, Japan
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  • Daisaku Ashikari,

    1. Department of Urology, Nihon University School of Medicine, Tokyo, Japan
    2. Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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  • Yasutaka Murata,

    1. Department of Urology, Nihon University School of Medicine, Tokyo, Japan
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  • Kenya Yamaguchi,

    1. Department of Urology, Nihon University School of Medicine, Tokyo, Japan
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  • Tomohiko Urano,

    1. Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
    2. Department of Geriatric Medicine, The University of Tokyo, Tokyo, Japan
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  • Tetsuya Fujimura,

    1. Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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  • Noboru Fukuda,

    1. Department of Advanced Medicine and Advanced Research Institute of Sciences and Humanities, Nihon University School of Medicine, Tokyo, Japan
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  • Masayoshi Soma,

    1. Division of General Medicine, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
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  • Takayoshi Watanabe,

    1. Chiba Cancer Center Research Institute, Chiba, Japan
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  • Hiroki Nagase,

    1. Chiba Cancer Center Research Institute, Chiba, Japan
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  • Satoshi Inoue,

    Corresponding author
    1. Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
    2. Department of Geriatric Medicine, The University of Tokyo, Tokyo, Japan
    3. Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan
    • Correspondence

      Satoshi Inoue, Department of Anti-Aging Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

      Tel: 81-3-5800-8834; Fax: +81-3-5800-9126;

      E-mail: INOUE-GER@h.u-tokyo.ac.jp

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  • Satoru Takahashi

    1. Department of Urology, Nihon University School of Medicine, Tokyo, Japan
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  • Funding information

    This work was supported by Grants of the Cell Innovation Program (to S. I.) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan; by the 2011–2015 Strategic Research Foundation for Private Universities (to M. S., D. O., K. F., N. F. and S. T.) from the MEXT-Supported Program; by Grants (to D. O., S. I., T. U. and S. T) from the Japan Society for the Promotion of Science, Japan; by the 2010 Research Grant of the 60th Anniversary Memorial Fund (to D. O.) from the Nihon University Medical Alumni Association; by the Young Researcher Promotion Grant (to D. O.) from The Japanese Urological Association; and by the Program for Promotion of Fundamental Studies in Health Sciences (S. I.), National Institute of Biomedical Innovation, Japan.

Abstract

Aberrant overexpression of ERG induced by the TMPRSS2-ERG gene fusion is likely involved in the development of prostate cancer. Synthetic pyrrole–imidazole (PI) polyamides recognize and attach to the minor groove of DNA with high affinity and specificity. In the present study, we designed a PI polyamide targeting TMPRSS2-ERG translocation breakpoints and assessed its effect on human prostate cancer cells. Our study identified that this PI polyamide repressed the cell and tumor growth of androgen-sensitive LNCaP prostate cancer cells. Targeting of these breakpoint sequences by PI polyamides could be a novel approach for the treatment of prostate cancer.

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