The Wilms tumor suppressor WT1 encodes a transcriptional activator of amphiregulin
The Wilms tumor suppressor WT1 encodes a transcriptional activator of amphiregulin
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DOI：
10.1016/s0092-8674(00)80053-7
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发表时间：
1999-09-03
期刊：
影响因子：
64.5
通讯作者：
Haber, DA
中科院分区：
文献类型：
--
作者：
Lee, SB;Huang, K;Haber, DA
WT1 编码与肾脏分化和肿瘤发生有关的锌指转录因子。在报告基因检测中，WT1 抑制富含 GC 和 To 的启动子的转录，但其生理目标仍不确定。我们利用与高密度寡核苷酸阵列的杂交来寻找表达在 WT1 诱导表达后发生改变的天然基因。 WT1 的主要目标是双调蛋白，表皮生长因子家族的成员。 WT1(-KTS) 同种型直接与双调蛋白启动子结合，导致有效的转录激活。胎儿肾脏发育过程中双调蛋白的体内表达谱反映了 WT1 本身的高度特异性模式，重组双调蛋白刺激胚胎小鼠肾脏器官培养物中的上皮分支。这些观察结果表明 WT1 在肾脏分化过程中作为转录调节因子的模型。
WT1 encodes a zinc finger transcription factor implicated in kidney differentiation and tumorigenesis. In reporter assays, WT1 represses transcription from GC- and To-rich promoters, but its physiological targets remain uncertain. We used hybridization to high-density oligonucleotide arrays to search for native genes whose expression is altered following inducible expression of WT1. The major target of WT1 was amphiregulin, a member of the epidermal growth factor family. The WT1(-KTS) isoform binds directly to the amphiregulin promoter, resulting in potent transcriptional activation. The in vivo expression profile of amphiregulin during fetal kidney development mirrors the highly specific pattern of WT1 itself, and recombinant Amphiregulin stimulates epithelial branching in organ cultures of embryonic mouse kidney. These observations suggest a model for WT1 as a transcriptional regulator during kidney differentiation.