Others TET2 repression by androgen hormone regulates global hydroxymethylation status and prostate cancer progression

Takayama, Ken-ichi  ,  Misawa, Aya  ,  Suzuki, Takashi  ,  Takagi, Kiyoshi  ,  Hayashizaki, Yoshihide  ,  Fujimura, Tetsuya  ,  Homma, Yukio  ,  Takahashi, Satoru  ,  Urano, Tomohiko  ,  Inoue, Satoshi

62015-09-25 , Nature Publishing Group , Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo , Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo , Department of Pathology, Graduate School of Medicine, Tohoku University , RIKEN Omics Science Center (OSC), RIKEN Yokohama Institute , RIKEN Preventive Medicine & Diagnosis Innovation Program , Department of Urology, Graduate School of Medicine, The University of Tokyo , Department of Urology, Nihon University School of Medicine , Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University
ISSN:2041-1723 (online)
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
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.


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