Universität zu Köln

Massberg, Desiree, Jovancevic, Nikolina, Offermann, Anne, Simon, Annika, Baniahmad, Aria, Perner, Sven, Pungsrinont, Thanakorn, Luko, Katarina, Philippou, Stathis, Ubrig, Burkhard, Heiland, Markus, Weber, Lea, Altmueller, Janine, Becker, Christian, Gisselmann, Guenter, Gelis, Lian and Hatt, Hanns (2016). The activation of OR51E1 causes growth suppression of human prostate cancer cells. Oncotarget, 7 (30). S. 48231 - 48250. ORCHARD PARK: IMPACT JOURNALS LLC. ISSN 1949-2553

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Massberg, Desiree UNSPECIFIED UNSPECIFIED UNSPECIFIED Jovancevic, Nikolina UNSPECIFIED UNSPECIFIED UNSPECIFIED Offermann, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Simon, Annika UNSPECIFIED UNSPECIFIED UNSPECIFIED Baniahmad, Aria UNSPECIFIED UNSPECIFIED UNSPECIFIED Perner, Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED Pungsrinont, Thanakorn UNSPECIFIED UNSPECIFIED UNSPECIFIED Luko, Katarina UNSPECIFIED UNSPECIFIED UNSPECIFIED Philippou, Stathis UNSPECIFIED UNSPECIFIED UNSPECIFIED Ubrig, Burkhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Heiland, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Weber, Lea UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Gisselmann, Guenter UNSPECIFIED UNSPECIFIED UNSPECIFIED Gelis, Lian UNSPECIFIED UNSPECIFIED UNSPECIFIED Hatt, Hanns UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-269551
DOI:	10.18632/oncotarget.10197
Journal or Publication Title:	Oncotarget
Volume:	7
Number:	30
Page Range:	S. 48231 - 48250
Date:	2016
Publisher:	IMPACT JOURNALS LLC
Place of Publication:	ORCHARD PARK
ISSN:	1949-2553
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROTEIN-COUPLED RECEPTOR; SIGNAL-TRANSDUCTION PATHWAYS; ANDROGEN RECEPTOR; OLFACTORY RECEPTOR; CELLULAR SENESCENCE; TUMOR-SUPPRESSOR; FATTY-ACIDS; RNA-SEQ; NEUROENDOCRINE CARCINOMAS; ENTEROCHROMAFFIN CELLS Multiple languages Oncology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26955