The transcription factor Net regulates the angiogenic switch
The transcription factor Net regulates the angiogenic switch
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DOI：
10.1101/gad.272503
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发表时间：
2003-09-15
影响因子：
10.5
通讯作者：
Wasylyk, B
中科院分区：
文献类型：
--
作者：
Zheng, H;Wasylyk, C;Wasylyk, B
血管生成是生理和病理过程的基础。尽管进行了大量的努力，但人们对调控血管生成的细胞内回路知之甚少。转录因子Net被RAS诱导的磷酸化激活，RAS是血管生成的间接调节因子。Net在小鼠发育早期的血管生成和血管生成部位都有表达，提示它可能在血管形成中发挥作用。我们在这里表明，在体内、体外和体外，Net的下调抑制了血管生成和血管内皮生长因子(VEGF)的表达。RAS激活的磷酸化网络(P-net)通过主要结合Sp1的-80至-53区域刺激小鼠血管内皮生长因子启动子。P-net和VEGF在野生型小鼠组织和人类肿瘤的血管生成过程中共同表达。我们得出结论，Net是一种血管生成的调节因子，在促血管生成分子的诱导下可以转换为激活剂。
Angiogenesis is fundamental to physiological and pathological processes. Despite intensive efforts, little is known about the intracellular circuits that regulate angiogenesis. The transcription factor Net is activated by phosphorylation induced by Ras, an indirect regulator of angiogenesis. Net is expressed at sites of vasculogenesis and angiogenesis during early mouse development, suggesting that it could have a role in blood vessel formation. We show here that down-regulation of Net inhibits angiogenesis and vascular endothelial growth factor (VEGF) expression in vivo, ex vivo, and in vitro. Ras-activated phosphorylated Net (P-Net) stimulates the mouse VEGF promoter through the -80 to -53 region that principally binds Sp1. P-Net and VEGF are coexpressed in angiogenic processes in wild-type mouse tissues and in human tumors. We conclude that Net is a regulator of angiogenesis that can switch to an activator following induction by pro-angiogenic molecules.