title: Urotensin-II receptor is over-expressed in colon cancer cell lines and in colon carcinoma in humans.
abstract: BACKGROUND
  Urotensin (U)-II receptor (UTR) has been previously reported to be over-expressed in a number of tumours. Whether UTR-related pathway plays a role in colon carcinogenesis is unknown.
  
  
  METHODS
  We evaluated UTR protein and mRNA expression in human epithelial colon cancer cell lines and in normal colon tissue, adenomatous polyps and colon cancer. U-II protein expression was assessed in cancer cell lines. Moreover, we evaluated the effects of U-II(4-11) (an UTR agonist), antagonists and knockdown of UTR protein expression through a specific shRNA, on proliferation, invasion and motility of human colon cancer cells.
  
  
  RESULTS
  Cancer cell lines expressed U-II protein and UTR protein and mRNA. By immunohistochemistry, UTR was expressed in 5-30% of epithelial cells in 45 normal controls, in 30-48% in 21 adenomatous polyps and in 65-90% in 48 colon adenocarcinomas. UTR mRNA expression was increased by threefold in adenomatous polyps and eightfold in colon cancer, compared with normal colon. U-II(4-11) induced a 20-40% increase in cell growth while the blockade of the receptor with specific antagonists caused growth inhibition of 20-40%. Moreover, the knock down of UTR with a shRNA or the inhibition of UTR with the antagonist urantide induced an approximately 50% inhibition of both motility and invasion.
  
  
  CONCLUSIONS
  UTR appears to be involved in the regulation of colon cancer cell invasion and motility. These data suggest that UTR-related pathway may play a role in colon carcinogenesis and that UTR may function as a target for therapeutic intervention in colon cancer.
authors.affiliation: Gastroenterology Unit, Department of Clinical and Experimental Medicine and Surgery, Second University of Naples, Naples, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Federico
authors.forename: Silvia
authors.initials: S
authors.lastname: Zappavigna
authors.forename: Marco
authors.initials: M
authors.lastname: Romano
authors.forename: Paolo
authors.initials: P
authors.lastname: Grieco
authors.forename: Amalia
authors.initials: A
authors.lastname: Luce
authors.forename: Monica
authors.initials: M
authors.lastname: Marra
authors.forename: Antonietta Gerarda
authors.initials: AG
authors.lastname: Gravina
authors.forename: Paola
authors.initials: P
authors.lastname: Stiuso
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: D'Armiento
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vitale
authors.forename: Concetta
authors.initials: C
authors.lastname: Tuccillo
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Carmela
authors.initials: C
authors.lastname: Loguercio
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003106:Colon / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003111:Colonic Polyps / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D055785:Gene Knockdown Techniques; D019073:HT29 Cells / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010446:Peptide Fragments / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D014579:Urotensins / Q000494:pharmacology
chemical_list: D010446:Peptide Fragments; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human; D014579:Urotensins; C029677:urotensin II
keywords: Colon cancer; urotensin-II; urotensin-II receptor