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Science. 2012 Dec 14;338(6113):1465-9. doi: 10.1126/science.1227604.

EZH2 oncogenic activity in castration-resistant prostate cancer cells is Polycomb-independent.

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1
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

Abstract

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.

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PMID:
23239736
PMCID:
PMC3625962
DOI:
10.1126/science.1227604
[Indexed for MEDLINE]
Free PMC Article

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