Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration
Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration
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DOI：
10.1101/gad.287404
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发表时间：
2004-06-15
影响因子：
10.5
通讯作者：
Winton, DJ
中科院分区：
文献类型：
--
作者：
Sansom, OJ;Reed, KR;Winton, DJ
尽管猿猴被认为是肠道中的肿瘤抑制基因，但这种抑制的确切机制仍有待确定。我们利用一种新的可诱导的Ahcre转基因系和一个loxp侧的Apc等位基因，表明Apc的缺失通过β -连环蛋白的核积累，急剧激活Wnt信号。巧合的是，它扰乱了分化、迁移、增殖和凋亡，使猿缺陷细胞保持“隐窝祖细胞样”表型。至关重要的是，我们首次在体内环境中确认了一系列Wnt靶标分子，并在相同的环境中确定了一系列新的候选靶标。
Although Ape is well characterized as a tumor-suppressor gene in the intestine, the precise mechanism of this suppression remains to be defined. Using a novel inducible Ahcre transgenic line in conjunction with a loxP-flanked Apc allele we, show that loss of Apc acutely activates Wnt signaling through the nuclear accumulation of beta-catenin. Coincidentally, it perturbs differentiation, migration, proliferation, and apoptosis, such that Ape-deficient cells maintain a "crypt progenitor-like" phenotype. Critically, for the first time we confirm a series of Wnt target molecules in an in vivo setting and also identify a series of new candidate targets within the same setting.