Foxl1 is a mesenchymal Modifier of Min in carcinogenesis of stomach and colon
Foxl1 is a mesenchymal Modifier of Min in carcinogenesis of stomach and colon
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DOI：
10.1101/gad.1260605
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发表时间：
2005-02-01
影响因子：
10.5
通讯作者：
Kaestner, KH
中科院分区：
文献类型：
--
作者：
Perreault, N;Sackett, SD;Kaestner, KH
Wnt/APC/β-catenin通路的组成性激活是胃肠道癌变过程中常见的起始事件。大肠腺瘤性息肉病（APC）基因的突变通过稳定β-连环蛋白和激活增殖控制中重要的靶点来上调Wnt信号传导。在这里，我们表明，间充质转录因子Foxl 1的损失导致显着增加的肿瘤多样性在Apc（Min）小鼠的结肠。Apc（Min/+）; Foxl 1（-/-）小鼠也发生了在Apc（Min）小鼠中未观察到的胃肿瘤。这些效应是由于Apc基因座的加速杂合性丢失（洛）导致的早期肿瘤发生引起的。Foxl 1是Min的第一个间充质修饰因子，在胃肠道肿瘤发生中起关键作用。
Constitutive activation of the Wnt/APC/beta-catenin pathway is a frequent initiating event in gastrointestinal carcinogenesis. Mutations in the Adenomatous Polyposis Coli (APC) gene up-regulate Wnt signaling by stabilizing beta-catenin and causing activation of targets important in proliferation control. Here we show that loss of the mesenchymal transcription factor Foxl1 leads to a marked increase in tumor multiplicity in the colon of Apc(Min) mice. Apc(Min/+);Foxl1(-/-) mice also develop gastric tumors not observed in Apc(Min) mice. These effects are caused by earlier tumor initiation due to accelerated loss of heterozygosity (LOH) at the Apc locus. Foxl1 is the first mesenchymal Modifier of Min and plays a key role in gastrointestinal tumorigenesis.