由于Mad2诱导的染色体不稳定导致在基因退出后肺瘤复发
Rocio Sotillo1, Juan-Manuel Schvartzman, Nicholas D Socci
1Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
由Mad2过度表达引起的染色体不稳定性并没有阻止最初的瘤回归,但显著增加了复发率. 这表明早期的不稳定性驱动癌症治疗后复发.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 遗传学 是一个遗传学.
背景情况:
- 瘤基因成描述了瘤基因抑制后的瘤细胞死亡,推动了向癌症治疗的发展.
- 固体瘤经常表现出染色体不稳定性,这是由于线粒体检查点路径放松调节.
- 染色体不稳定对瘤基因成的影响仍然未被探索.
研究的目的:
- 为了研究染色体不稳定性对Kras驱动的肺瘤中的癌基因成的影响.
- 为了确定短暂的线粒体检查点基因过度表达是否影响瘤抑制后的瘤复发.
主要方法:
- 过度表达小鼠中的线粒检查点基因Mad2,诱导染色体不稳定.
- 在Kras驱动的肺瘤中抑制Kras以评估初始回归.
- 监测瘤复发率,并分析复发瘤的 ploidy 和路径激活.
主要成果:
- 过度表达Mad2和诱导的染色体不稳定性没有影响Kras抑制后Kras驱动的肺瘤的初始回归.
- 经历过渡性Mad2过度表达和染色体不稳定的瘤显示出明显增加的复发率.
- 复发的瘤具有高度的形形状,具有多种激活促生殖途径的多样性.
结论:
- 早期染色体不稳定可能不会阻碍初始治疗反应,但显著促进瘤复发.
- 在复发性瘤中,积体和多样化的促生殖途径激活表明克服向治疗的机制.
- 这项研究强调染色体不稳定是癌症治疗失败和复发的关键因素.
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