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Updated: Mar 18, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
The activation of OR51E1 causes growth suppression of human prostate cancer cells
Désirée Maßberg1, Nikolina Jovancevic1, Anne Offermann2
1Department of Cell Physiology, Ruhr-University Bochum, Bochum, Germany.
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.
Insights
Olfactory receptor OR51E1 activation suppresses prostate cancer (PCa) cell growth and androgen receptor signaling. This suggests OR51E1 is a potential therapeutic target for advanced prostate cancer, offering new hope for treatment resistance.
Area of Science:
- Oncology
- Molecular Biology
- G-protein coupled receptor signaling
Background:
- Prostate cancer (PCa) growth is androgen receptor (AR) dependent, making androgen-deprivation therapy (ADT) a standard treatment.
- Treatment resistance and disease recurrence due to castration resistance remain significant challenges in advanced PCa.
- G-protein coupled receptors (GPCRs) are implicated in PCa physiology and represent potential therapeutic targets.
Purpose of the Study:
- To investigate the role of olfactory receptors (ORs), specifically OR51E1 and OR51E2, in prostate cancer.
- To determine the effect of OR51E1 activation on PCa cell growth and AR signaling pathways.
- To explore the potential of OR51E1 as a therapeutic target for advanced prostate cancer.
Main Methods:
- Gene expression of OR51E1 and OR51E2 in human PCa tissue was analyzed using RNA-Seq and RT-PCR.
- Subcellular localization of OR51E1 and OR51E2 proteins was determined in human prostate tissue.
- PCa cell lines (LNCaP) were treated with OR51E1 agonists (nonanoic acid, decanoic acid) and control compounds to assess effects on cell growth, protein kinase phosphorylation, AR target gene expression, and cellular senescence.
Main Results:
- OR51E1 and OR51E2 gene expression was verified in human PCa tissue.
- The OR51E1 agonist nonanoic acid (NA) suppressed LNCaP cell growth, induced protein kinase phosphorylation, and reduced androgen-mediated AR target gene expression.
- NA treatment induced cellular senescence in PCa cells, accompanied by decreased E2F1 mRNA levels. Decanoic acid, another OR51E1 agonist, also induced senescence, while non-activating compounds did not.
Conclusions:
- OR51E1 plays a significant role in regulating prostate cancer cell growth and AR-mediated signaling.
- Activation of OR51E1 can induce cellular senescence and inhibit PCa cell proliferation.
- OR51E1 represents a promising therapeutic target for overcoming castration resistance and treating advanced prostate cancer.
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