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| Item Type: | Article |
|---|---|
| Title: | The activation of OR51E1 causes growth suppression of human prostate cancer cells |
| Creators Name: | Maßberg, D., Jovancevic, N., Offermann, A., Simon, A., Baniahmad, A., Perner, S., Pungsrinont, T., Luko, K., Philippou, S., Ubrig, B., Heiland, M., Weber, L., Altmüller, J., Becker, C., Gisselmann, G., Gelis, L. and Hatt, H. |
| 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. |
| Keywords: | OR51E1, Proliferation, Prostate Cancer, Cellular Senescence, Androgen Receptor |
| Source: | Oncotarget |
| ISSN: | 1949-2553 |
| Publisher: | Impact Journals |
| Volume: | 7 |
| Number: | 30 |
| Page Range: | 48231-48249 |
| Date: | 26 July 2016 |
| Additional Information: | Copyright © 2016 Maßberg et al. This work is licensed under a Creative Commons Attribution 4.0 License. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/ or send a letter to Creative Commons, PO Box 1866, Mountain View, CA 94042, USA. |
| Official Publication: | https://doi.org/10.18632/oncotarget.10197 |
| PubMed: | View item in PubMed |
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