Tristetraprolin regulates expression of VEGF and tumorigenesis in human colon cancer
Tristetraprolin regulates expression of VEGF and tumorigenesis in human colon cancer
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DOI：
10.1002/ijc.24847
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发表时间：
2010-04-15
影响因子：
6.4
通讯作者：
Park, Jeong Woo
中科院分区：
文献类型：
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作者：
Lee, Hyun Hee;Son, Young Joon;Park, Jeong Woo
Tristetraprolin（TIP）是一种富含AU的元件结合蛋白，可调节mRNA的稳定性。在这里，我们报告TIP抑制人结肠癌细胞的生长在体内和体外通过调节血管内皮生长因子（VEGF）的表达。TTP蛋白在结肠腺癌组织中的表达明显低于正常粘膜和腺瘤组织。VEGF在结肠腺癌中的表达高于正常粘膜和腺瘤。RNA干扰抑制UP的表达可使培养的人结肠癌细胞中VEGF的表达增加，而TTP的过表达可使其表达减少，TIP的高表达可使与VEGF mRNA 3'末端富含AU的元件（ARE）相连的荧光素酶的表达水平降低。过表达TIP的Colo 320/TTP细胞在体外生长缓慢，皮下移植到裸鼠体内形成小肿瘤。这些发现表明TIP作为结肠癌细胞中VEGF基因表达的负调节剂，表明其可用作治疗结肠癌的新治疗剂。
Tristetraprolin (TIP) is an AU-rich element-binding protein that regulates mRNA stability. Here, we report that TIP suppress the growth of human colon cancer cells both in vivo and in vitro by regulating of the expression of vascular endothelial growth factor (VEGF). TTP protein expression in human colonic tissues was markedly decreased in colonic adenocarcinoma compared with in normal mucosa and adenoma. VEGF expression was higher in colonic adenocarcinoma than in normal mucosa and adenoma. Specific inhibition of UP expression by RNA-interference increased the expression of VEGF in cultured human colon cancer cells, and TTP overexpression markedly decreased it. In addition, elevated expression of TIP decreased the expression level of luciferase linked to a 3' terminal AU-rich element (ARE) of VEGF mRNA. Colo320/TTP cells overexpressing TIP grew slowly in vitro and became tumors small in size when xenografted s.c into nude mice. These findings demonstrate that TIP acts as a negative regulator of VEGF gene expression in colon cancer cells, suggesting that it can be used as novel therapeutic agent to treat colon cancer.