在抵抗割的前列腺癌细胞中,EZH2的致癌活性是Polycomb独立的
Kexin Xu1, Zhenhua Jeremy Wu, Anna C Groner
1Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Science (New York, N.Y.)
|December 15, 2012
概括
增强性雌激素同类基因2 (EZH2) 通过协同激活转录因子,而不是仅仅通过基因沉默驱动割抵抗性前列腺癌. 针对这种非PRC2功能为晚期前列腺癌提供了新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 表观遗传调节剂正在成为癌症治疗的关键目标.
- 增强性基因同类2 (EZH2) 的增强剂,是Polycomb抑制复合体2 (PRC2) 的组成部分,通常通过基因基因甲基化对基因沉默起作用.
- 抗割前列腺癌 (CRPC) 是一个重大的治疗挑战.
研究的目的:
- 调查EZH2在割抵抗性前列腺癌中的致癌作用.
- 为了确定EZH2在CRPC中的功能是否依赖于其正规的转录抑制活性.
- 探索针对晚期前列腺癌中EZH2的新型治疗策略.
主要方法:
- 在抵抗割的前列腺癌细胞系中分析EZH2功能.
- 研究EZH2与转录因子的相互作用,包括雄激素受体.
- 评估EZH2化和甲基转移酶活性对其致癌功能的影响.
主要成果:
- EZH2通过一种独立于其转录抑制器功能的机制促进了抵抗割的前列腺癌的进展.
- EZH2 作为关键转录因子,特别是雄激素受体的联合激活剂.
- 这种联合激活器功能取决于EZH2酸化,需要一个完整的甲基转移酶域.
结论:
- 在CRPC中EZH2的致癌活性涉及作为协活性剂的非正规作用.
- 准EZH2的非PRC2联合激活器功能是一个有前途的治疗途径.
- 这种方法可能有效治疗转移性,抗激素前列腺癌.
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