Oncotarget

Research Papers:

The activation of OR51E1 causes growth suppression of human prostate cancer cells

Désirée Maßberg _, Nikolina Jovancevic, Anne Offermann, Annika Simon, Aria Baniahmad, Sven Perner, Thanakorn Pungsrinont, Katarina Luko, Stathis Philippou, Burkhard Ubrig, Markus Heiland, Lea Weber, Janine Altmüller, Christian Becker, Günter Gisselmann, Lian Gelis and Hanns Hatt

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Oncotarget. 2016; 7:48231-48249. https://doi.org/10.18632/oncotarget.10197

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Abstract

Désirée Maßberg1, Nikolina Jovancevic1, Anne Offermann2, Annika Simon1, Aria Baniahmad3, Sven Perner2, Thanakorn Pungsrinont3, Katarina Luko3, Stathis Philippou4, Burkhard Ubrig5, Markus Heiland5, Lea Weber1, Janine Altmüller6, Christian Becker6, Günter Gisselmann1, Lian Gelis1,7, Hanns Hatt1

1Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany

2Pathology of the University Hospital of Luebeck and the Leibniz Research Center Borstel, Luebeck and Borstel, Germany

3Institute of Human Genetics, Jena University Hospital, Jena, Germany

4Institute for Pathology und Cytology, Augusta-Kranken-Anstalt gGmbH Bochum, Bochum, Germany

5Clinic for Urology, Augusta-Kranken-Anstalt gGmbH Bochum, Bochum, Germany

6Cologne Center for Genomics, University of Köln, Köln, Germany

7Present address: Global Drug Discovery - Clinical Sciences, Bayer Pharma AG, Wuppertal, Germany

Correspondence to:

Désirée Maßberg, email: [email protected]

Keywords: OR51E1, proliferation, prostate cancer, cellular senescence, androgen receptor

Received: December 21, 2015     Accepted: June 06, 2016     Published: June 21, 2016

ABSTRACT

The development of prostate cancer (PCa) is regulated by the androgen-dependent activity of the androgen receptor (AR). Androgen-deprivation therapy (ADT) is therefore the gold standard treatment to suppress malignant progression of PCa. Nevertheless, due to the development of castration resistance, recurrence of disease after initial response to ADT is a major obstacle to successful treatment. As G-protein coupled receptors play a fundamental role in PCa physiology, they might represent promising alternative or combinatorial targets for advanced diseases. Here, we verified gene expression of the olfactory receptors (ORs) OR51E1 [prostate-specific G-protein coupled receptor 2 (PSGR2)] and OR51E2 (PSGR) in human PCa tissue by RNA-Seq analysis and RT-PCR and elucidated the subcellular localization of both receptor proteins in human prostate tissue. The OR51E1 agonist nonanoic acid (NA) leads to the phosphorylation of various protein kinases and growth suppression of the PCa cell line LNCaP. Furthermore, treatment with NA causes reduction of androgen-mediated AR target gene expression. Interestingly, NA induces cellular senescence, which coincides with reduced E2F1 mRNA levels. In contrast, treatment with the structurally related compound 1-nonanol or the OR2AG1 agonist amyl butyrate, neither of which activates OR51E1, did not lead to reduced cell growth or an induction of cellular senescence. However, decanoic acid, another OR51E1 agonist, also induces cellular senescence. Thus, our results suggest the involvement of OR51E1 in growth processes of PCa cells and its impact on AR-mediated signaling. These findings provide novel evidences to support the functional importance of ORs in PCa pathogenesis.


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