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

2 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Odorant Receptors
Testosterone
Prostatic Neoplasms
Aromatase
Phosphopyruvate Hydratase
G-Protein-Coupled Receptors
Cell Cycle Checkpoints
GTP-Binding Proteins
Computer Simulation
Prostate
Cell Survival
Up-Regulation
Cell Line
19-hydroxy-4-androstene-3,17-dione
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A testosterone metabolite 19-hydroxyandrostenedione induces neuroendocrine trans-differentiation of prostate cancer cells via an ectopic olfactory receptor. / Abaffy, Tatjana; Bain, James R.; Muehlbauer, Michael J.; Spasojevic, Ivan; Lodha, Shweta; Bruguera, Elisa; O'Neal, Sara K.; Kim, So Young; Matsunami, Hiroaki.

In: Frontiers in Oncology, Vol. 8, No. MAY, 162, 28.05.2018.

Research output: Contribution to journalArticle

Abaffy, T, Bain, JR, Muehlbauer, MJ, Spasojevic, I, Lodha, S, Bruguera, E, O'Neal, SK, Kim, SY & Matsunami, H 2018, 'A testosterone metabolite 19-hydroxyandrostenedione induces neuroendocrine trans-differentiation of prostate cancer cells via an ectopic olfactory receptor', Frontiers in Oncology, vol. 8, no. MAY, 162. https://doi.org/10.3389/fonc.2018.00162
Abaffy, Tatjana ; Bain, James R. ; Muehlbauer, Michael J. ; Spasojevic, Ivan ; Lodha, Shweta ; Bruguera, Elisa ; O'Neal, Sara K. ; Kim, So Young ; Matsunami, Hiroaki. / A testosterone metabolite 19-hydroxyandrostenedione induces neuroendocrine trans-differentiation of prostate cancer cells via an ectopic olfactory receptor. In: Frontiers in Oncology. 2018 ; Vol. 8, No. MAY.
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