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

Marie Odile Guimond, Marie Claude Battista, Fatemeh Nikjouitavabi, Maude Carmel, Véronique Barres, Alexandre A. Doueik, Ladan Fazli, Martin Gleave, Robert Sabbagh, Nicole Gallo-Payet

Research output: Contribution to journalArticle

21 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1057-1068
Number of pages12
JournalProstate
Volume73
Issue number10
DOIs
Publication statusPublished - Jul 2013

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Keywords

  • angiotensin
  • AT receptor
  • cancer
  • human prostate
  • primary cell culture
  • proliferation

ASJC Scopus subject areas

  • Urology
  • Oncology

Cite this

Guimond, M. O., Battista, M. C., Nikjouitavabi, F., Carmel, M., Barres, V., Doueik, A. A., ... Gallo-Payet, N. (2013). Expression and role of the angiotensin II AT2 receptor in human prostate tissue: In search of a new therapeutic option for prostate cancer. Prostate, 73(10), 1057-1068. https://doi.org/10.1002/pros.22653