Id2 drives differentiation and suppresses tumor formation in the intestinal epithelium
Id2 drives differentiation and suppresses tumor formation in the intestinal epithelium
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DOI：
10.1158/0008-5472.can-04-2095
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发表时间：
2004-10-15
期刊：
影响因子：
11.2
通讯作者：
Iavarone, A
中科院分区：
文献类型：
--
作者：
Russell, RG;Lasorella, A;Iavarone, A
致癌信号在多种肿瘤类型中升高Id 2的表达。当解除调节时，Id 2使肿瘤抑制蛋白视网膜母细胞瘤、p107和p130失活。在这里，我们报告了一种新的和意想不到的肿瘤抑制功能的Id 2在肠上皮细胞。首先，在小鼠中Id 2的基因消融防止在形成隐窝-绒毛单位时肠上皮细胞的分化和细胞周期停滞。后来，这些发育异常向肿瘤转化发展，并完全转化。Id 2无效肿瘤含有严重的发育不良和化生病变，并表达异常量的β-连环蛋白。因此，我们的数据是第一个建立基本的螺旋-环-螺旋抑制剂在驱动分化中的直接需求，并定义了视网膜母细胞瘤结合蛋白Id 2在预防肿瘤形成中的意外作用。
Oncogenic signals elevate expression of Id2 in multiple tumor types. When deregulated, Id2 inactivates the tumor suppressor proteins retinoblastoma, p107, and p130. Here, we report a novel and unexpected tumor inhibitory function of Id2 in the intestinal epithelium. First, genetic ablation of Id2 in the mouse prevents differentiation and cell cycle arrest of enterocytes at the time of formation of the crypt-villus unit. Later, these developmental abnormalities evolve toward neoplastic transformation with complete penetrance. Id2-null tumors contain severe dysplastic and metaplastic lesions and express aberrant amounts of beta-catenin. Thus, our data are the first to establish a direct requirement of basic helix-loop-helix inhibitors in driving differentiation and define an unexpected role for the retinoblastoma-binding protein Id2 in preventing tumor formation.