雌激素诱导的活性氧物种,通过表观遗传重编程,导致乳腺癌细胞的增长
Priti Roy1, Ramji Kandel1, Neha Sawant1
1Department of Environmental Toxicology, Texas Tech University, Lubbock, TX, 79409, USA.
Molecular and cellular endocrinology
|October 20, 2023
概括
雌激素通过增加活性氧物种 (ROS) 来促进乳腺癌的生长,这些物种改变了表观遗传基因调节. 一种抗氧化剂N-乙囊可以逆转这些效应,这表明乳腺癌的新治疗点.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 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:
- 乳腺癌是妇女死亡的主要原因,雌激素暴露是关键风险因素.
- 雌激素代谢产生反应性氧物种 (ROS),与致癌有关,但精确的分子机制尚不清楚.
- 表观遗传修饰,包括DNA甲基化和基因素修饰,是基因表达的关键调节者.
研究的目的:
- 通过异常的表观遗传调节基因表达和重编程,调查雌激素诱导的ROS是否有助于乳腺癌细胞生长.
- 评估抗氧化剂N-乙囊 (NAC) 对雌激素诱导的ROS,细胞生长,基因表达和基因素修饰的影响.
主要方法:
- 对雌激素敏感的人类乳腺癌细胞系 (MCF-7和T47D) 用单独的17β-雌激醇 (E2) 和乙醇 (DES) 以及NAC进行治疗.
- 对细胞增殖 (MTT测定),细胞循环进展,表观遗传调节者的基因表达,以及基因素修饰 (H3激活/抑制标记) 的评估影响.
主要成果:
- 通过清除ROS,NAC显著抑制了E2和DES诱导的乳腺癌细胞生长.
- E2和DES改变了参与DNA甲基化和基因组修饰的基因表达,以及基因组H3标记的变化.
- 纳克治疗恢复了表观遗传调节基因的正常表达,并逆转了异常的基因组修饰.
结论:
- 雌激素通过一种涉及ROS依赖的表观遗传机制调节的机制促进乳腺癌细胞的增殖.
- 雌激素诱导的ROS导致表观遗传重编程,特别是改变组织蛋白标记,从而驱动癌细胞生长.
- 向ROS和相关的表观遗传变化为雌激素驱动的乳腺癌提供了潜在的治疗策略.
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