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Tristetraprolin regulates expression of VEGF and tumorigenesis in human colon cancer

✍ Scribed by Hyun Hee Lee; Young Joon Son; Won Hyeok Lee; Young Woo Park; Seoung Wan Chae; Wha Ja Cho; Young Min Kim; Hye-Jeong Choi; Dae Hwa Choi; Seok Won Jung; Young Joo Min; Soon Eun Park; Byung Ju Lee; Hee Jeong Cha; Jeong Woo Park

Publisher
John Wiley and Sons
Year
2009
Tongue
French
Weight
675 KB
Volume
126
Category
Article
ISSN
0020-7136

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✦ Synopsis

Abstract

Tristetraprolin (TTP) is an AU‐rich element‐binding protein that regulates mRNA stability. Here, we report that TTP 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 TTP 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 TTP decreased the expression level of luciferase linked to a 3′ terminal AU‐rich element (ARE) of VEGF mRNA. Colo320/TTP cells overexpressing TTP grew slowly in vitro and became tumors small in size when xenografted s.c into nude mice. These findings demonstrate that TTP 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.

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