title: Gene expression study of Aurora-A reveals implication during bladder carcinogenesis and increasing values in invasive urothelial cancer.
abstract: OBJECTIVE
  Urothelial carcinoma is a frequent and aggressive cancer. We wanted to gain better insight into the early molecular mechanisms of bladder carcinogenesis by evaluating Aurora-A gene expression, which is implicated in genomic stability and essential for mitosis.
  
  
  METHODS
  This study, using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), analyzed the expression levels of three selected genes in dissected tissues from normal bladder, noninvasive cancers, and muscle-invasive bladder carcinomas (n = 49). We compared gene expression levels of three genes (Aurora-A, and as control uroplakin II (UPII) and TBP, respectively) at different stages of bladder cancer. We used multivariate analysis, receiver operating characteristic curves and the nonparametric Mann-Whitney test.
  
  
  RESULTS
  The expression of Aurora-A gene studied was significantly deregulated, with an increasing level in cancer versus normal tissue Aurora-A. This development was linear. Aurora-A was already deregulated in early stages of carcinogenesis (pTa/pT1) (P = 0.0004) and displayed even more deregulation in muscle-invasive stages (pT2 to pT4). Immunohistochemistry performed on the same samples using Aurora-A antibody confirmed results of RT-PCR, with statistically significant values when comparing m-RNA expression and immunohistochemical values (P = 0.0001).
  
  
  CONCLUSIONS
  This study highlights the fact that Aurora-A gene expression is already strongly deregulated in early stages of urothelial carcinoma with abnormal expression, and might be considered a biomarker of tumor aggression. The increase in Aurora-A expression might provide further information regarding the behavior of bladder cancer in daily practice.
authors.affiliation: CNRS UMR 8149, Faculté de Pharmacie, Paris V, Paris, France. evacomperat@yahoo.fr
authors.forename: Eva
authors.initials: E
authors.lastname: Compérat
authors.forename: Ivan
authors.initials: I
authors.lastname: Bièche
authors.forename: Delphine
authors.initials: D
authors.lastname: Dargère
authors.forename: Ingrid
authors.initials: I
authors.lastname: Laurendeau
authors.forename: Annick
authors.initials: A
authors.lastname: Vieillefond
authors.forename: Gérard
authors.initials: G
authors.lastname: Benoit
authors.forename: Michel
authors.initials: M
authors.lastname: Vidaud
authors.forename: Philippe
authors.initials: P
authors.lastname: Camparo
authors.forename: Fréderique
authors.initials: F
authors.lastname: Capron
authors.forename: Catherine
authors.initials: C
authors.lastname: Verret
authors.forename: Olivier
authors.initials: O
authors.lastname: Cussenot
authors.forename: Pierre
authors.initials: P
authors.lastname: Bedossa
authors.forename: Valérie
authors.initials: V
authors.lastname: Paradis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D064127:Aurora Kinases; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*; D019459:Urothelium / Q000473:pathology
chemical_list: D012333:RNA, Messenger; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases