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EZH2 Oncogenic Activity in Castration-Resistant Prostate Cancer Cells Is Polycomb-lndependent

机译：去势抵抗前列腺癌细胞中的EZH2致癌活性是多梳依赖性的。

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摘要

Epigenetic regulators represent a promising new class of therapeutic targets for cancer. Enhancer of zeste homolog 2 (EZH2), a subunit of Polycomb repressive complex 2 (PRC2), silences gene expression via its histone methyltransferase activity. We found that the oncogenic function of EZH2 in cells of castration-resistant prostate cancer is independent of its role as a transcriptional repressor. Instead, it involves the ability of EZH2 to act as a coactivator for critical transcription factors including the androgen receptor. This functional switch is dependent on phosphorylation of EZH2 and requires an intact methyltransferase domain. Hence, targeting the non-PRC2 function of EZH2 may have therapeutic efficacy for treating metastatic, hormone-refractory prostate cancer.
机译：表观遗传调节剂代表了一种有前途的新型癌症治疗靶标。 Zeste同系物2（EZH2）的增强子，Polycomb阻抑复合物2（PRC2）的一个亚基，通过其组蛋白甲基转移酶活性使基因表达沉默。我们发现EZH2在去势抵抗性前列腺癌细胞中的致癌功能与其作为转录阻遏物的作用无关。相反，它涉及EZH2充当关键转录因子（包括雄激素受体）的共激活因子的能力。此功能开关取决于EZH2的磷酸化，需要完整的甲基转移酶结构域。因此，靶向EZH2的非PRC2功能可能具有治疗转移性激素难治性前列腺癌的疗效。

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  • 来源
    《Science》 |2012年第6113期|1465-1469|共5页
  • 作者

    Kexin Xu; Zhenhua Jeremy Wu; Anna C. Groner; Housheng Hansen He; Changmeng Cai; Rosina T. Lis; Xiaoqiu Wu; Edward C. Stack; Massimo Loda; Tao Liu; Han Xu; Laura Cato; James E. Thornton; Richard I. Gregory; Colm Morrissey; Robert L. Vessella; Rodolfo Montironi; Cristina Magi-Galluzzi; Philip W. Kantoff; Steven P. Balk; X. Shirley Liu; Myles Brown;

  • 作者单位

    Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA,Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA;

    Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA,Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, MA 02115, USA;

    Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA,Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA;

    Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA,Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA,Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, MA 02115, USA;

    Hematology-Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA;

    Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA,Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02115, USA,Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA;

    Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA,Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02115, USA;

    Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA,Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02115, USA,Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA;

    Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA,Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02115, USA,Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA,Division of Cancer Studies, King's College London, London SE1 8UB, UK;

    Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA,Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, MA 02115, USA;

    Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA,Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, MA 02115, USA;

    Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA,Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA;

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA,Stem Cell Program, Children's Hospital, Boston, MA 02115, USA;

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA,Stem Cell Program, Children's Hospital, Boston, MA 02115, USA;

    Department of Urology, University of Washington Medical Center, Seattle, WA 98195, USA;

    Department of Urology, University of Washington Medical Center, Seattle, WA 98195, USA,Puget Sound VA Health Care System, Seattle, WA 98108, USA;

    Section of Pathological Anatomy, Polytechnic University of Marche Region, United Hospitals, 60126 Torrette, Ancona, Italy;

    Pathology and Laboratory Medicine Institute, Glickman Urological and Kidney Institute, Department of Cancer Biology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA;

    Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA;

    Hematology-Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA;

    Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA,Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, MA 02115, USA;

    Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA,Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 入库时间 2022-08-18 02:53:42

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