删除myc可以挽救小肠中的Apc缺陷
Owen J Sansom1, Valerie S Meniel, Vanesa Muncan
1The Beatson Institute, Garscube Estate, Glasgow G61 1BD, UK. o.sansom@beatson.gla.ac.uk
Nature
|March 23, 2007
概括
Myc的丧失挽救了由Apc基因删除引起的肠道异常,揭示了Myc是早期结直肠癌发展的关键调解者. 这一发现突显了Myc在APC损失后Wnt通路激活中的关键作用.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 细菌腺瘤多样性 (APC) 基因突变是家族腺瘤多样性 (FAP) 和零星结直肠癌的核心.
- 通过APC的非激活,可导致β-catenin-Tcf4转录复合物的构成性激活,这是结直肠癌的一个关键事件.
- 原型瘤基因c-MYC是Wnt通路的标,但在肠道中APC损失后,其具体作用尚不清楚.
研究的目的:
- 为了研究APC损失后Myc在肠道中的作用.
- 为了确定Myc是否介导与Apc删除相关的表型.
- 阐明Myc在APC损失后的Wnt目标基因激活中的功能.
主要方法:
- 在成年小肠中同时删除 Apc 和 Myc 基因.
- 肠道分化,迁移,增殖和亡的表型分析.
- 使用阵列分析进行基因表达分析,以评估Wnt目标基因激活.
主要成果:
- Myc的损失挽救了由Apc删除引起的异常分化,迁移,增殖和亡表型.
- 尽管核β-catenin的持续高水平,但救援发生了.
- 发现Myc在APC丢失后对大多数Wnt目标基因的激活至关重要.
结论:
- 在APC损失后,Myc在肠道瘤的早期阶段起到关键的调解作用.
- 这些发现确立了Myc作为Apc缺陷结直肠癌中Wnt途径的关键下游效应因子.
- 针对Myc可能为具有APC突变的结直肠癌提供治疗策略.
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