A testosterone metabolite 19-hydroxyandrostenedione induces neuroendocrine trans-differentiation of prostate cancer cells via an ectopic olfactory receptor

Tatjana Abaffy, James R. Bain, Michael J. Muehlbauer, Ivan Spasojevic, Shweta Lodha, Elisa Bruguera, Sara K. O'Neal, So Young Kim, Hiroaki Matsunami

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish (US)
Article number162
JournalFrontiers in Oncology
Volume8
Issue numberMAY
DOIs
StatePublished - May 28 2018

Keywords

  • 19-hydroxyandrostenedione
  • Agonists
  • Neuroendocrine trans-differentiation
  • Neuron-specific enolase
  • OR51E2
  • Olfactory receptor
  • PSGR
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Abaffy, T., Bain, J. R., Muehlbauer, M. J., Spasojevic, I., Lodha, S., Bruguera, E., O'Neal, S. K., Kim, S. Y., & Matsunami, H. (2018). A testosterone metabolite 19-hydroxyandrostenedione induces neuroendocrine trans-differentiation of prostate cancer cells via an ectopic olfactory receptor. Frontiers in Oncology, 8(MAY), [162]. https://doi.org/10.3389/fonc.2018.00162