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

dc.contributor.author Abaffy, Tatjana
dc.contributor.author Bain, James R
dc.contributor.author Bruguera, Elisa
dc.contributor.author Kim, So Young
dc.contributor.author Lodha, Shweta
dc.contributor.author Matsunami, Hiroaki
dc.contributor.author Muehlbauer, Michael J
dc.contributor.author O'Neal, Sara K
dc.contributor.author Spasojević, Ivan
dc.date.accessioned 2018-07-05T13:43:29Z
dc.date.available 2018-07-05T13:43:29Z
dc.date.issued 2018-01
dc.identifier.issn 2234-943X
dc.identifier.issn 2234-943X
dc.identifier.uri https://hdl.handle.net/10161/17219
dc.description.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.
dc.language eng
dc.relation.ispartof Frontiers in oncology
dc.relation.isversionof 10.3389/fonc.2018.00162
dc.subject 19-hydroxyandrostenedione
dc.subject OR51E2
dc.subject PSGR
dc.subject agonists
dc.subject neuroendocrine trans-differentiation
dc.subject neuron-specific enolase
dc.subject olfactory receptor
dc.subject prostate cancer
dc.title A Testosterone Metabolite 19-Hydroxyandrostenedione Induces Neuroendocrine Trans-Differentiation of Prostate Cancer Cells via an Ectopic Olfactory Receptor.
dc.type Journal article
dc.date.updated 2018-07-05T13:43:26Z
pubs.begin-page 162
pubs.issue MAY
pubs.organisational-group School of Medicine
pubs.organisational-group Duke
pubs.organisational-group Center for the Study of Aging and Human Development
pubs.organisational-group Institutes and Centers
pubs.organisational-group Medicine, Endocrinology, Metabolism, and Nutrition
pubs.organisational-group Medicine
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Sarah Stedman Nutrition & Metabolism Center
pubs.organisational-group Duke Molecular Physiology Institute
pubs.organisational-group Molecular Genetics and Microbiology
pubs.organisational-group Basic Science Departments
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Neurobiology
pubs.organisational-group Duke Science & Society
pubs.organisational-group Initiatives
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Duke Institute for Brain Sciences
pubs.organisational-group University Institutes and Centers
pubs.organisational-group Medicine, Medical Oncology
pubs.publication-status Published
pubs.volume 8
duke.contributor.orcid Matsunami, Hiroaki|0000-0002-8850-2608


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