title: Tristetraprolin regulates expression of VEGF and tumorigenesis in human colon cancer.
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.
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan, Korea.
authors.forename: Hyun Hee
authors.initials: HH
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan, Korea.
authors.forename: Young Joon
authors.initials: YJ
authors.lastname: Son
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan, Korea.
authors.forename: Won Hyeok
authors.initials: WH
authors.lastname: Lee
authors.affiliation: Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejon, Korea.
authors.forename: Young Woo
authors.initials: YW
authors.lastname: Park
authors.affiliation: Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Seoung Wan
authors.initials: SW
authors.lastname: Chae
authors.affiliation: Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
authors.forename: Wha Ja
authors.initials: WJ
authors.lastname: Cho
authors.affiliation: Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
authors.forename: Young Min
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
authors.forename: Hye-Jeong
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
authors.forename: Dae Hwa
authors.initials: DH
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
authors.forename: Seok Won
authors.initials: SW
authors.lastname: Jung
authors.affiliation: 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.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Min
authors.affiliation: Department of Anesthesia and Pain Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
authors.forename: Soon Eun
authors.initials: SE
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan, Korea.|Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
authors.forename: Byung Ju
authors.initials: BJ
authors.lastname: Lee
authors.affiliation: Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
authors.forename: Hee Jeong
authors.initials: HJ
authors.lastname: Cha
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan, Korea.|Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
authors.forename: Jeong Woo
authors.initials: JW
authors.lastname: Park
mesh_terms: 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
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051816:Tristetraprolin; D042461:Vascular Endothelial Growth Factor A