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

Authors

  • Marie-Odile Guimond,

    1. Endocrinology Division, Department of Medicine, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada
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  • Marie-Claude Battista,

    1. Endocrinology Division, Department of Medicine, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada
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  • Fatemeh Nikjouitavabi,

    1. Endocrinology Division, Department of Medicine, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada
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  • Maude Carmel,

    1. Urology Division, Department of Surgery, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada
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  • Véronique Barres,

    1. Centre de recherche du centre hospitalier de l'Université de Montréal (CR-CHUM) and Institut du cancer de Montréal, Quebec, Canada
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  • Alexandre A. Doueik,

    1. Department of Pathology, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada
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  • Ladan Fazli,

    1. The Prostate Centre at Vancouver General Hospital, British Columbia, Canada
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  • Martin Gleave,

    1. The Prostate Centre at Vancouver General Hospital, British Columbia, Canada
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  • Dr. Robert Sabbagh,

    Corresponding author
    1. Urology Division, Department of Surgery, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada
    • Urology Division, Department of Surgery, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, 3001, 12th Ave North, Sherbrooke, Quebec, Canada J1H 5N4.
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  • Nicole Gallo-Payet

    1. Endocrinology Division, Department of Medicine, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada
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  • Robert Sabbagh and Nicole-Gallo-Payet are co-senior authors.

  • Disclosure statement: Each author certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (e.g., employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: none.

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

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