MYC促进了WNT-骨髓母细胞瘤小鼠模型的积极生长和转移
Rachel Hartley1, Timothy N Phoenix1,2
1Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, Ohio, USA.
Developmental neuroscience
|August 6, 2023
概括
这项研究表明,在小鼠模型中,增加Myc信号促进脑髓母细胞瘤的生长和转移. 低风险子组WNT-MB在Myc被激活时显示出改变的细胞外基质和细胞粘附途径.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 骨髓母细胞瘤 (MB) 是最常见的儿科大脑恶性瘤,有四个不同的分子子组 (WNT,SHH,组3,组4) 呈现不同的预后.
- 在CTNNB1突变中,WNT-MB具有低风险,而3MB组 (GRP3-MB) 则具有高风险,经常转移,并与MYC表达升高有关.
研究的目的:
- 为了比较低风险WNT-MB和高风险GRP3-MB的模型系统.
- 为了确定影响MB预后的瘤和微环境相互作用.
主要方法:
- 对WNT-MB和GRP3-MB模型系统进行比较分析.
- 在小鼠WNT-MB模型中引入MycT58A.
- 分析与细胞外基因矩阵 (ECM) 调节,细胞粘附和免疫系统信号相关的基因组.
主要成果:
- 与GRP3-MB相比,WNT-MB在ECM调节和细胞粘附基因组中表现出丰富.
- 在WNT-MB模型中的外源MycT58A表达加速了瘤生长并诱导了转移.
- MycT58A表达导致ECM调节,细胞粘附和免疫系统信号通路的下调.
结论:
- 增加Myc信号可以驱动WNT-MB小鼠模型的生长和转移.
- 瘤内在的Myc信号影响瘤的微环境,包括免疫相互作用.
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