title: The activation of OR51E1 causes growth suppression of human prostate cancer cells.
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.
authors.affiliation: Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Désirée
authors.initials: D
authors.lastname: Maßberg
authors.affiliation: Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Nikolina
authors.initials: N
authors.lastname: Jovancevic
authors.affiliation: Pathology of the University Hospital of Luebeck and the Leibniz Research Center Borstel, Luebeck and Borstel, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Offermann
authors.affiliation: Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Simon
authors.affiliation: Institute of Human Genetics, Jena University Hospital, Jena, Germany.
authors.forename: Aria
authors.initials: A
authors.lastname: Baniahmad
authors.affiliation: Pathology of the University Hospital of Luebeck and the Leibniz Research Center Borstel, Luebeck and Borstel, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
authors.affiliation: Institute of Human Genetics, Jena University Hospital, Jena, Germany.
authors.forename: Thanakorn
authors.initials: T
authors.lastname: Pungsrinont
authors.affiliation: Institute of Human Genetics, Jena University Hospital, Jena, Germany.
authors.forename: Katarina
authors.initials: K
authors.lastname: Luko
authors.affiliation: Institute for Pathology und Cytology, Augusta-Kranken-Anstalt gGmbH Bochum, Bochum, Germany.
authors.forename: Stathis
authors.initials: S
authors.lastname: Philippou
authors.affiliation: Clinic for Urology, Augusta-Kranken-Anstalt gGmbH Bochum, Bochum, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Ubrig
authors.affiliation: Clinic for Urology, Augusta-Kranken-Anstalt gGmbH Bochum, Bochum, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Heiland
authors.affiliation: Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Lea
authors.initials: L
authors.lastname: Weber
authors.affiliation: Cologne Center for Genomics, University of Köln, Köln, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Altmüller
authors.affiliation: Cologne Center for Genomics, University of Köln, Köln, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Becker
authors.affiliation: Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Gisselmann
authors.affiliation: Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.|Present address: Global Drug Discovery - Clinical Sciences, Bayer Pharma AG, Wuppertal, Germany.
authors.forename: Lian
authors.initials: L
authors.lastname: Gelis
authors.affiliation: Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Hanns
authors.initials: H
authors.lastname: Hatt
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D016922:Cellular Senescence; D018450:Disease Progression; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000378:metabolism*; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection
chemical_list: C410798:AR protein, human; D009363:Neoplasm Proteins; C510734:OR51E1 protein, human; D011944:Receptors, Androgen; D043562:Receptors, G-Protein-Coupled
keywords: OR51E1; androgen receptor; cellular senescence; proliferation; prostate cancer