REPRESSION OF THE INSULIN-LIKE GROWTH FACTOR-II GENE BY THE WILMS-TUMOR SUPPRESSOR WT1
REPRESSION OF THE INSULIN-LIKE GROWTH FACTOR-II GENE BY THE WILMS-TUMOR SUPPRESSOR WT1
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DOI：
10.1126/science.1323141
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发表时间：
1992-07-31
期刊：
影响因子：
56.9
通讯作者：
RAUSCHER, FJ
中科院分区：
文献类型：
--
作者：
DRUMMOND, IA;MADDEN, SL;RAUSCHER, FJ
Wilms肿瘤抑制基因wt 1编码锌指DNA结合蛋白，WT 1，其作为转录抑制物起作用。胎儿有丝分裂原胰岛素样生长因子II（IGF-II）在肾母细胞瘤中过表达，可能在肿瘤进展中具有自分泌作用。在瞬时转染试验中，主要的胎儿IGF-II启动子被定义为相对于转录起始位点，从核苷酸-295到+135的区域。WT 1结合到该区域的多个位点，并在体内作为IGF-II转录的有效阻遏物发挥作用。最大抑制依赖于转录起始位点两侧WT 1结合位点的存在。这些研究结果提供了一个在肾母细胞瘤中IGF-II过表达的分子基础，并表明WT 1通过限制发育中脊椎动物肾脏中胎儿生长因子的产生来负调节胚基细胞增殖。
The Wilms tumor suppressor gene wt1 encodes a zinc finger DNA binding protein, WT1, that functions as a transcriptional repressor. The fetal mitogen insulin-like growth factor II (IGF-II) is overexpressed in Wilms tumors and may have autocrine effects in tumor progression. The major fetal IGF-II promoter was defined in transient transfection assays as a region spanning from nucleotides -295 to +135, relative to the transcription start site. WT1 bound to multiple sites in this region and functioned as a potent repressor of IGF-II transcription in vivo. Maximal repression was dependent on the presence of WT1 binding sites on each side of the transcriptional initiation site. These findings provide a molecular basis for overexpression of IGF-II in Wilms tumors and suggest that WT1 negatively regulates blastemal cell proliferation by limiting the production of a fetal growth factor in the developing vertebrate kidney.