Tristetraprolin regulates expression of VEGF and tumorigenesis in human colon cancer

doi:10.1002/ijc.24847

. 2010 Apr 15;126(8):1817-1827.

doi: 10.1002/ijc.24847.

Tristetraprolin regulates expression of VEGF and tumorigenesis in human colon cancer

Hyun Hee Lee¹, Young Joon Son¹, Won Hyeok Lee¹, Young Woo Park², Seoung Wan Chae³, Wha Ja Cho⁴, Young Min Kim⁵, Hye-Jeong Choi⁵, Dae Hwa Choi⁶, Seok Won Jung⁷, Young Joo Min^{4

7}, Soon Eun Park⁸, Byung Ju Lee^{1

4}, Hee Jeong Cha⁵, Jeong Woo Park^{1

4}

Affiliations

¹ Department of Biological Sciences, University of Ulsan, Ulsan, Korea.
² Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejon, Korea.
³ Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
⁴ Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
⁵ Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
⁶ Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
⁷ Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
⁸ Department of Anesthesia and Pain Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.

PMID: 19697322
DOI: 10.1002/ijc.24847

Tristetraprolin regulates expression of VEGF and tumorigenesis in human colon cancer

Hyun Hee Lee et al. Int J Cancer. 2010.

. 2010 Apr 15;126(8):1817-1827.

doi: 10.1002/ijc.24847.

Authors

Affiliations

¹ Department of Biological Sciences, University of Ulsan, Ulsan, Korea.
² Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejon, Korea.
³ Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
⁴ Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
⁵ Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
⁶ Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
⁷ Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
⁸ Department of Anesthesia and Pain Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.

PMID: 19697322
DOI: 10.1002/ijc.24847

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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Tristetraprolin regulates expression of VEGF and tumorigenesis in human colon cancer

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Tristetraprolin regulates expression of VEGF and tumorigenesis in human colon cancer

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