Chemoprevention trials for prostate cancer by androgen receptor or androgen synthesis inhibition have proven ineffective. Recently, it has been demonstrated that the histone methlytransferase, EZH2 is deregulated in mouse and human high-grade prostatic intraepithelial neoplasia (HG-PIN). Using preclinical mouse and human models of prostate cancer, we demonstrate that genetic and chemical disruption of EZH2 expression and catalytic activity reversed the HG-PIN phenotype. Furthermore, inhibition of EZH2 function was associated with loss of cellular proliferation and induction of Tp53-dependent senescence. Together, these data provide provocative evidence for EZH2 as an actionable therapeutic target toward prevention of prostate cancer.

中文翻译：

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Ezh2 放松管制是预防前列腺癌的可行治疗目标的证据

通过雄激素受体或雄激素合成抑制进行的前列腺癌化学预防试验已证明无效。最近，已经证明组蛋白甲基转移酶 EZH2 在小鼠和人类高级别前列腺上皮内瘤变 (HG-PIN) 中失调。使用前列腺癌的临床前小鼠和人体模型，我们证明了 EZH2 表达和催化活性的遗传和化学破坏逆转了 HG-PIN 表型。此外，EZH2 功能的抑制与细胞增殖的丧失和 Tp53 依赖性衰老的诱导有关。总之，这些数据为 EZH2 作为预防前列腺癌的可操作治疗靶点提供了有说服力的证据。