title: Expression and role of the angiotensin II AT2 receptor in human prostate tissue: in search of a new therapeutic option for prostate cancer.
abstract: BACKGROUND
  Evidence shows that angiotensin II type 1 receptor (AT1R) blockers may be associated with improved outcome in prostate cancer patients. It has been proposed that part of this effect could be due to angiotensin II type 2 receptor (AT2R) activation, the only active angiotensin II receptor in this situation. This study aimed to characterize the localization and expression of AT2R in prostate tissues and to assess its role on cell morphology and number in prostatic epithelial cells in primary culture.
  
  
  METHODS
  AT2R and its AT2R-interacting protein (ATIP) expression were assessed on non-tumoral and tumoral human prostate using tissue microarray immunohistochemistry, binding assay, and Western blotting. AT2R effect on cell number was measured in primary cultures of epithelial cells from non-tumoral human prostate.
  
  
  RESULTS
  AT2R was localized at the level of the acinar epithelial layer and its expression decreased in cancers with a Gleason score 6 or higher. In contrast, ATIP expression increased with cancer progression. Treatment of primary cell cultures from non-tumoral prostate tissues with C21/M024, a selective AT2R agonist, alone or in co-incubation with losartan, an AT1R antagonist, significantly decreased cell number compared to untreated cells.
  
  
  CONCLUSIONS
  AT2R and ATIP are present in non-tumoral human prostate tissues and differentially regulated according to Gleason score. The decrease in non-tumoral prostate cell number upon selective AT2R stimulation suggests that AT2R may have a protective role against prostate cancer development. Treatment with a selective AT2R agonist could represent a new approach for prostate cancer prevention or for patients on active surveillance.
authors: Endocrinology Division, Department of Medicine, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors: Marie-Odile
authors: MO
authors: Guimond
authors: Marie-Claude
authors: MC
authors: Battista
authors: Fatemeh
authors: F
authors: Nikjouitavabi
authors: Maude
authors: M
authors: Carmel
authors: Véronique
authors: V
authors: Barres
authors: Alexandre A
authors: AA
authors: Doueik
authors: Ladan
authors: L
authors: Fazli
authors: Martin
authors: M
authors: Gleave
authors: Robert
authors: R
authors: Sabbagh
authors: Nicole
authors: N
authors: Gallo-Payet
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D011467:Prostate / Q000187:drug effects / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists / Q000378:metabolism*; D046888:Tissue Array Analysis; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; C474762:MTUS1 protein, human; D044139:Receptor, Angiotensin, Type 2; D025521:Tumor Suppressor Proteins; D019808:Losartan