Tristetraprolin regulates expression of VEGF and tumorigenesis in human colon cancer.
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.
Lee
Hyun Hee
HH
Department of Biological Sciences, University of Ulsan, Ulsan, Korea.
Son
Young Joon
YJ
Department of Biological Sciences, University of Ulsan, Ulsan, Korea.
Lee
Won Hyeok
WH
Department of Biological Sciences, University of Ulsan, Ulsan, Korea.
Park
Young Woo
YW
Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejon, Korea.
Chae
Seoung Wan
SW
Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Cho
Wha Ja
WJ
Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
Kim
Young Min
YM
Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
Choi
Hye-Jeong
HJ
Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
Choi
Dae Hwa
DH
Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
Jung
Seok Won
SW
Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
Min
Young Joo
YJ
Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.|Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
Park
Soon Eun
SE
Department of Anesthesia and Pain Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
Lee
Byung Ju
BJ
Department of Biological Sciences, University of Ulsan, Ulsan, Korea.|Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
Cha
Hee Jeong
HJ
Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
Park
Jeong Woo
JW
Department of Biological Sciences, University of Ulsan, Ulsan, Korea.|Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D000236:Adenoma / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009367:Neoplasm Staging; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D051816:Tristetraprolin / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051816:Tristetraprolin; D042461:Vascular Endothelial Growth Factor A