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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Abaffy, T; Bain, JR; Muehlbauer, MJ; Spasojevic, I; Lodha, S; Bruguera, E; O'Neal, SK; Kim, SY; Matsunami, H

Published Date

  • 2018

Published In

Volume / Issue

  • 8 /

Start / End Page

  • 162 -

PubMed ID

  • 29892571

Pubmed Central ID

  • PMC5985834

International Standard Serial Number (ISSN)

  • 2234-943X

Digital Object Identifier (DOI)

  • 10.3389/fonc.2018.00162


  • eng

Conference Location

  • Switzerland