A Testosterone Metabolite 19-Hydroxyandrostenedione Induces Neuroendocrine Trans-Differentiation of Prostate Cancer Cells via an Ectopic Olfactory Receptor.

Abstract

Olfactory receptor OR51E2, also known as a Prostate Specific G-Protein Receptor, is highly expressed in prostate cancer but its function is not well understood. Through in silico and in vitro analyses, we identified 24 agonists and 1 antagonist for this receptor. We detected that agonist 19-hydroxyandrostenedione, a product of the aromatase reaction, is endogenously produced upon receptor activation. We characterized the effects of receptor activation on metabolism using a prostate cancer cell line and demonstrated decreased intracellular anabolic signals and cell viability, induction of cell cycle arrest, and increased expression of neuronal markers. Furthermore, upregulation of neuron-specific enolase by agonist treatment was abolished in OR51E2-KO cells. The results of our study suggest that OR51E2 activation results in neuroendocrine trans-differentiation. These findings reveal a new role for OR51E2 and establish this G-protein coupled receptor as a novel therapeutic target in the treatment of prostate cancer.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.3389/fonc.2018.00162

Publication Info

Abaffy, Tatjana, James R Bain, Michael J Muehlbauer, Ivan Spasojevic, Shweta Lodha, Elisa Bruguera, Sara K O'Neal, So Young Kim, et al. (2018). A Testosterone Metabolite 19-Hydroxyandrostenedione Induces Neuroendocrine Trans-Differentiation of Prostate Cancer Cells via an Ectopic Olfactory Receptor. Frontiers in oncology, 8(MAY). p. 162. 10.3389/fonc.2018.00162 Retrieved from https://hdl.handle.net/10161/17219.

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Scholars@Duke

Bain

James R. Bain

Professor in Medicine
Spasojevic

Ivan Spasojevic

Associate Professor in Medicine
Kim

So Young Kim

Associate Research Professor in Molecular Genetics and Microbiology

I serve as Director of the Duke Functional Genomics Core Facility, where our central mission is to provide resources for high-throughput analysis of gene function and small molecule screens for drug discovery. Our core works with Duke investigators to provide the expertise, infrastructure and libraries necessary for these screens and can collaborate on all stages of the screening project, including study design, assay optimization and data analysis. The facility also provides services for custom cell line engineering using techniques including CRISPR knockouts/knockins, RNAi gene suppression and ORF expression. Our lab is also interested in collaborating with investigators to develop and improve existing methodologies to enhance the utility of functional genomics tools within the lab. 

I am also the Director of the Duke Microbiome Core Facility, which supports the research of investigators seeking to uncover the roles that microbiomes play in human health and the environment. The core provides assistance with study design, sample management, DNA extractions, NGS library prep and data analysis. The lab is also interested in developing new techniques and analysis tools to better assess microbiome composition across a range of sample types.


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