title: Tristetraprolin downregulates the expression of both VEGF and COX-2 in human colon cancer.
abstract: OBJECTIVE
  Although both VEGF and COX-2 are important factors influencing angiogenesis (and thus, carcinogenesis), the regulation of these factors in carcinogenesis remains poorly understood. The aim is to investigate the effects of tristetraprolin, an AU-rich element-binding protein on the expression of VEGF and COX-2 in human colon cancer cells.
  
  
  METHODS
  Expression of TTP, VEGF and COX-2 in the resected colorectal cancer surgical specimens were analyzed by immunohistochemistry. Colon cancer cells were transfected with luciferase reporter linked to 3'UTR of VEGF or COX-2. The effects of TTP overexpression on the expression of VEGF, COX-2 and luciferase were determined by semiquantitative RT-PCR or luciferase assay.
  
  
  RESULTS
  Immunohistochemical staining of resected colorectal cancer surgical specimens revealed that TTP expression was low in cancer cells but high in non-malignant mucosa. In contrast, the expression of both COX-2 and VEGF was high in cancer cells and very low in non-malignant mucosa. TTP overexpression markedly decreased the expression of both COX-2 and VEGF in colon cancer cells. In addition, TTP inhibited the expression of luciferase linked to 3'UTR of COX-2 or VEGF mRNA.
  
  
  CONCLUSIONS
  TTP inhibits the expression of both VEGF and COX-2 and reduced expression of TTP may be responsible for the increased expression of COX-2 and VEGF in human colorectal cancer.
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.forename: Hyun Hee
authors.initials: HH
authors.lastname: Lee
authors.forename: Seoung Wan
authors.initials: SW
authors.lastname: Chae
authors.forename: Wha Ja
authors.initials: WJ
authors.lastname: Cho
authors.forename: Young Min
authors.initials: YM
authors.lastname: Kim
authors.forename: Hye-Jeong
authors.initials: HJ
authors.lastname: Choi
authors.forename: Dae Hwa
authors.initials: DH
authors.lastname: Choi
authors.forename: Seok Won
authors.initials: SW
authors.lastname: Jung
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Min
authors.forename: Byung Ju
authors.initials: BJ
authors.lastname: Lee
authors.forename: Soon Eun
authors.initials: SE
authors.lastname: Park
authors.forename: Jeong Woo
authors.initials: JW
authors.lastname: Park
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D003110:Colonic Neoplasms / Q000737:chemistry*; D051546:Cyclooxygenase 2 / Q000032:analysis* / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D051816:Tristetraprolin / Q000032:analysis / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis* / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D051816:Tristetraprolin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C497552:ZFP36 protein, human; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human