作为针对c-Myc的治疗策略,BET代蛋白抑制是一种治疗策略
Jake E Delmore1, Ghayas C Issa, Madeleine E Lemieux
1Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
Cell
|September 6, 2011
概括
通过JQ1通过odomain抑制准MYC转录,有效地降低了Myc依赖基因的调节. 这种方法对多发性骨髓瘤和其他由MYC驱动的癌症具有治疗前景.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症遗传学 癌症遗传学
背景情况:
- MYC瘤基因驱动许多人类癌症,但直接的治疗策略仍然难以捉摸.
- MYC在癌症发病过程中的作用需要新的方法来准其致癌功能.
研究的目的:
- 研究抑制调节转录的原蛋白蛋白的潜力,作为调节MYC活动的策略.
- 评估小分子代胺抑制剂JQ1在向MYC转录及其下游效应方面的有效性.
主要方法:
- 利用JQ1,一种选择性原体抑制剂,向涉及转录调节的BET原体蛋白.
- 评估了BET抑制对MYC转录和全基因组Myc依赖基因表达的影响.
- 在多发性骨髓瘤的实验模型中评估了JQ1的抗增殖作用.
主要成果:
- JQ1选择性地抑制BET基蛋白蛋白质,导致MYC转录的下调.
- 全基因组分析显示,在BET抑制后,Myc依赖基因的广泛下调.
- 在多发性骨髓瘤模型中,JQ1表现出强大的抗增殖作用,诱导细胞循环停止和衰老.
结论:
- BET基蛋白蛋白是MYC转录的关键调节者.
- JQ1有效地准MYC驱动的转录,并在多发性骨髓瘤的临床前模型中表现出治疗潜力.
- 抑制BETodomain代表了对MYC驱动的恶性瘤的有前途的治疗策略.
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