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 language | English (US) |
|---|---|
| Article number | 162 |
| Journal | Frontiers in Oncology |
| Volume | 8 |
| Issue number | MAY |
| DOIs | |
| State | Published - May 28 2018 |
| Externally published | Yes |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - A testosterone metabolite 19-hydroxyandrostenedione induces neuroendocrine trans-differentiation of prostate cancer cells via an ectopic olfactory receptor
AU - Abaffy, Tatjana
AU - Bain, James R.
AU - Muehlbauer, Michael J.
AU - Spasojevic, Ivan
AU - Lodha, Shweta
AU - Bruguera, Elisa
AU - O'Neal, Sara K.
AU - Kim, So Young
AU - Matsunami, Hiroaki
PY - 2018/5/28
Y1 - 2018/5/28
N2 - 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.
AB - 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.
KW - 19-hydroxyandrostenedione
KW - Agonists
KW - Neuroendocrine trans-differentiation
KW - Neuron-specific enolase
KW - Olfactory receptor
KW - OR51E2
KW - Prostate cancer
KW - PSGR
UR - http://www.scopus.com/inward/record.url?scp=85047660018&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047660018&partnerID=8YFLogxK
U2 - 10.3389/fonc.2018.00162
DO - 10.3389/fonc.2018.00162
M3 - Article
AN - SCOPUS:85047660018
VL - 8
JO - Frontiers in Oncology
JF - Frontiers in Oncology
SN - 2234-943X
IS - MAY
M1 - 162
ER -