title: Angiotensin-2 receptors (AT1-R and AT2-R), new prognostic factors for renal clear-cell carcinoma?
abstract: BACKGROUND
  The growth factor Angiotensin-2 signals through Angiotensin receptor type 1 (AT1-R) in a broad range of cell types and tumours and through the type-2 receptor (AT2-R) in a more restricted group of cell types. Although numerous forms of cancer have been shown to overexpress AT1-R, expression of AT1-R and AT2-R by human renal clear-cell carcinoma (RCCC) is not well understood. In this study, the expression of both angiotensin receptors was quantified in a retrospective series of RCCC and correlated with prognostic factors.
  
  
  METHODS
  Angiotensin receptor type 1 and AT2-R expressions were quantified on tumour tissues by immunohistochemistry (IHC), western blot and quantitative reverse transcriptase PCR (qRT-PCR). IHC results were correlated to Fuhrman's grade and patient progression-free survival (PFS).
  
  
  RESULTS
  A total of 84 RCCC were analysed. By IHC, AT1-R and AT2-R were expressed to a greater level in high-grade tumours (AT1-R: P<0.001, AT2-R: P<0.001). Univariate analysis showed a correlation between PFS and AT1-R or AT2-R expression (P=0.001). By multivariate analysis, only AT2-R expression correlated with PFS (HR 1.021, P=0.006) and cancer stage (P<0.001). By western blot, AT1-R and AT1-R were also found to be overexpressed in higher Fuhrman's grade (P<0.01 and P=0.001 respectively). By qRT-PCR, AT1-R but not AT2-R mRNA were downregulated (P=0.001 and P=0.118, respectively).
  
  
  CONCLUSIONS
  Our results show that AT1-R and AT2-R proteins are overexpressed in the most aggressive forms of RCCC and that AT2-R expression correlates with PFS. AT1-R or AT2-R blockage could, therefore, offer novel directions for anti-RCCC therapy.
authors.affiliation: CNRS UMR6061/IFR140, Faculté de Médecine Université de Rennes 1, 2 avenue du professeur Léon Bernard, CS34317, 35043 Rennes Cedex, France.
authors.forename: T
authors.initials: T
authors.lastname: Dolley-Hitze
authors.forename: F
authors.initials: F
authors.lastname: Jouan
authors.forename: B
authors.initials: B
authors.lastname: Martin
authors.forename: S
authors.initials: S
authors.lastname: Mottier
authors.forename: J
authors.initials: J
authors.lastname: Edeline
authors.forename: O
authors.initials: O
authors.lastname: Moranne
authors.forename: P
authors.initials: P
authors.lastname: Le Pogamp
authors.forename: M-A
authors.initials: MA
authors.lastname: Belaud-Rotureau
authors.forename: J-J
authors.initials: JJ
authors.lastname: Patard
authors.forename: N
authors.initials: N
authors.lastname: Rioux-Leclercq
authors.forename: C
authors.initials: C
authors.lastname: Vigneau
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000737:chemistry / Q000401:mortality*; D018572:Disease-Free Survival; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000737:chemistry / Q000401:mortality*; D015999:Multivariate Analysis; D011379:Prognosis; D044140:Receptor, Angiotensin, Type 1 / Q000032:analysis*; D044139:Receptor, Angiotensin, Type 2 / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D057911:Angiotensin Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2