Expression and role of the angiotensin II AT2 receptor in human prostate tissue: In search of a new therapeutic option for prostate cancer

• Published in: The Prostate 2013-07, Vol.73 (10), p.1057-1068
• Main Authors: Guimond, Marie-Odile, Battista, Marie-Claude, Nikjouitavabi, Fatemeh, Carmel, Maude, Barres, Véronique, Doueik, Alexandre A., Fazli, Ladan, Gleave, Martin, Sabbagh, Robert, Gallo-Payet, Nicole
• Format: Article
• Language: English
• Subjects: angiotensin; Angiotensin II Type 1 Receptor Blockers - pharmacology; Angiotensin II Type 1 Receptor Blockers - therapeutic use; AT2 receptor; cancer; Cell Proliferation - drug effects; human prostate; Humans; Losartan - pharmacology; Losartan - therapeutic use; Male; primary cell culture; proliferation; Prostate - drug effects; Prostate - metabolism; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Receptor, Angiotensin, Type 2 - agonists; Receptor, Angiotensin, Type 2 - metabolism; Tissue Array Analysis; Tumor Suppressor Proteins - metabolism
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.22653

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. Prostate 73: 1057–1068, 2013. © 2013 Wiley Periodicals, Inc.