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Abstract

Modulation of epigenetic patterns has promising efficacy for treating cancer. 5-Hydroxymethylated cytosine (5-hmC) is an epigenetic mark potentially important in cancer. Here we report that 5-hmC is an epigenetic hallmark of prostate cancer (PCa) progression. A member of the ten–eleven translocation (TET) proteins, which catalyse the oxidation of methylated cytosine (5-mC) to 5-hmC, TET2, is repressed by androgens in PCa. Androgen receptor (AR)-mediated induction of the miR-29 family, which targets TET2, are markedly enhanced in hormone refractory PCa (HRPC) and its high expression predicts poor outcome of PCa patients. Furthermore, decreased expression of miR-29b results in reduced tumour growth and increased TET2 expression in an animal model of HRPC. Interestingly, global 5-hmC modification regulated by miR-29b represses FOXA1 activity. A reduction in 5-hmC activates PCa-related key pathways such as mTOR and AR. Thus, DNA modification directly links the TET2-dependent epigenetic pathway regulated by AR to 5-hmC-mediated tumour progression.UTokyo Research掲載「前立腺癌に対してホルモン療法が効きづらくなる理由」 URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/why-hormone-therapy-becomes-ineffective-against-prostate-cancer.html

UTokyo Research "Why hormone therapy becomes ineffective against prostate cancer" URI: http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/why-hormone-therapy-becomes-ineffective-against-prostate-cancer.html

Journal

  • Nature communications

    Nature communications (6), 8219, 2015-09-25

    Nature Publishing Group

Codes

  • NII Article ID (NAID)
    120006348519
  • NII NACSIS-CAT ID (NCID)
    AA12645905
  • Text Lang
    ENG
  • Article Type
    journal article
  • ISSN
    2041-1723
  • Data Source
    IR 
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