雄激素受体调节一个独特的转录程序在雄激素独立的前列腺癌
Qianben Wang1, Wei Li, Yong Zhang
1Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
Cell
|July 28, 2009
概括
雄激素受体 (AR) 驱动前列腺癌的生长,即使没有雄激素. 在晚期癌症中,AR激活特定的细胞循环基因,促进瘤进展和独立生长.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 前列腺癌的进展包括从依赖雄激素的状态转变为依赖雄激素的独立状态.
- 雄激素受体 (AR) 在两个阶段都起着关键作用,但其在先进的独立癌症中的功能尚未完全理解.
研究的目的:
- 定义直接依赖AR的目标基因,并阐明AR在抗雄激素独立前列腺癌细胞中的功能.
- 在晚期前列腺癌中研究AR介导基因调节的机制.
主要方法:
- 在雌激素依赖和非雌激素依赖的癌细胞中生成AR依赖基因表达特征.
- 针对AR细胞组分析,在全基因组范围内绘制AR结合部位的图.
- 在基因增强剂中分析表观遗传标记 (基因组H3K4甲基化) 和转录因子结合 (FoxA1).
主要成果:
- AR选择性地调节M阶段细胞循环基因,包括UBE2C,在雄激素独立细胞中,与雄激素依赖细胞不同.
- 在UBE2C增强剂的表观遗传修饰,如H3K4甲基化和FoxA1结合,促进AR结合和UBE2C激活在雌激素独立细胞中.
- 在雌激素独立的前列腺癌中,AR执行了独特的基因表达程序,推动了扩散.
结论:
- 雄激素受体 (AR) 在驱动雄激素独立前列腺癌生长方面发挥着至关重要的,独特的作用.
- 特定增强剂的表观遗传调节决定了AR在晚期前列腺癌中的功能.
- 针对这种独特的AR程序可能为致命的前列腺癌提供新的治疗策略.
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