Cystic renal neoplasia following conditional inactivation of Apc in mouse renal tubular epithelium
Cystic renal neoplasia following conditional inactivation of Apc in mouse renal tubular epithelium
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DOI：
10.1074/jbc.m410697200
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发表时间：
2005-02-04
影响因子：
4.8
通讯作者：
Williams, BO
中科院分区：
文献类型：
--
作者：
Qian, CN;Knol, J;Williams, BO
Wnt/β-连环蛋白信号传导的改变与肾脏发育异常和肿瘤发生有关。为了更深入地了解这些改变的影响，我们创建了携带特异性肾上皮中Apc肿瘤抑制基因的条件性缺失的小鼠。正如预期的那样，Apc的丧失导致肾上皮中β-连环蛋白水平的增加。这些小鼠中的大多数在出生后不久死亡，并且在组织学上发现多个肾囊肿。考试这些动物很少能活到成年。对这些成人的分析显示，严重的囊性肾与肾腺瘤的存在有关。我们的研究结果证实了Wnt/β-catenin信号传导在肾脏发育中的适当调节的重要作用，并提供了该途径失调可以启动肾脏肿瘤发生的证据。
Alterations in Wnt/beta-catenin signaling have been linked to abnormal kidney development and tumorigenesis. To gain more insights into the effects of these alterations, we created mice carrying a conditional deletion of the Apc tumor suppressor gene specifically in the renal epithelium. As expected, the loss of Apc leads to increased levels of beta-catenin protein in renal epithelium. Most of these mice die shortly after birth, and multiple kidney cysts were found upon, histological. examination. Only rarely did these animals survive to adulthood. Analysis of these adults revealed severely cystic kidneys associated with the presence of renal adenomas. Our results confirm an important role for proper regulation of Wnt/beta-catenin signaling in renal development and provide evidence that dysregulation of the pathway can initiate tumorigenesis in the kidney.