Please use this identifier to cite or link to this item:
https://doi.org/10.18632/oncotarget.10197
Title: | The activation of OR51E1 causes growth suppression of human prostate cancer cells | Authors: | 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 Hatt, H |
Keywords: | amyl butyrate androgen receptor butyric acid derivative G protein coupled receptor messenger RNA nonanoic acid nonanol prostate specific G protein coupled receptor prostate specific G protein coupled receptor 2 protein kinase RNA transcription factor E2F1 unclassified drug androgen receptor AR protein, human G protein coupled receptor OR51E1 protein, human tumor protein Article cancer cell cancer inhibition cancer tissue cell aging cell proliferation cellular distribution controlled study enzyme linked immunosorbent assay enzyme phosphorylation gene expression genetic transfection human human cell human tissue immunocytochemistry immunohistochemistry LNCaP cell line male plasmid prostate cancer protein expression protein localization reverse transcription polymerase chain reaction RNA isolation RNA sequence Western blotting biosynthesis castration resistant prostate cancer disease exacerbation genetics metabolism pathology phosphorylation physiology prostate tumor signal transduction tumor cell line Cell Line, Tumor Cell Proliferation Cellular Senescence Disease Progression Humans Male Neoplasm Proteins Phosphorylation Prostatic Neoplasms Prostatic Neoplasms, Castration-Resistant Receptors, Androgen Receptors, G-Protein-Coupled Signal Transduction Transfection |
Issue Date: | 2016 | Citation: | 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, Hatt, H (2016). The activation of OR51E1 causes growth suppression of human prostate cancer cells. Oncotarget 7 (30) : 48231-48249. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.10197 | Rights: | Attribution 4.0 International | Abstract: | The development of prostate cancer (PCa) is regulated by the androgendependent 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 androgenmediated 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. | Source Title: | Oncotarget | URI: | https://scholarbank.nus.edu.sg/handle/10635/179968 | ISSN: | 19492553 | DOI: | 10.18632/oncotarget.10197 | Rights: | Attribution 4.0 International |
Appears in Collections: | Staff Publications Elements |
Show full item record
Files in This Item:
File | Description | Size | Format | Access Settings | Version | |
---|---|---|---|---|---|---|
10_18632_oncotarget_10197.pdf | 7.17 MB | Adobe PDF | OPEN | None | View/Download |
This item is licensed under a Creative Commons License