Tristetraprolin regulates expression of VEGF and tumorigenesis in human colon cancer

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.