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PMID: 19389702 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Activation of an olfactory receptor inhibits proliferation of prostate cancer cells.

The Journal of biological chemistry ·Vol. 284 ·No. 24 ·2009-06-12 ·Pages 16218-16225

Neuhaus EM, Zhang W, Gelis L, Deng Y, Noldus J, Hatt H

Abstract

Olfactory receptors (ORs) are expressed not only in the sensory neurons of the olfactory epithelium, where they detect volatile substances, but also in various other tissues where their potential functions are largely unknown. Here, we report the physiological characterization of human OR51E2, also named prostate-specific G-protein-coupled receptor (PSGR) due to its reported up-regulation in prostate cancer. We identified androstenone derivatives as ligands for the recombinant receptor. PSGR can also be activated with the odorant beta-ionone. Activation of the endogenous receptor in prostate cancer cells by the identified ligands evoked an intracellular Ca2+ increase. Exposure to beta-ionone resulted in the activation of members of the MAPK family and inhibition of cell proliferation. Our data give support to the hypothesis that because PSGR signaling could reduce growth of prostate cancer cells, specific receptor ligands might therefore be potential candidates for prostate cancer treatment.

MeSH Terms
Androsterone/metabolism,pharmacology Calcium/metabolism Cell Division/drug effects,physiology Cell Line, Tumor Humans JNK Mitogen-Activated Protein Kinases/metabolism Kidney/cytology Ligands Male Neoplasm Proteins/genetics,metabolism Norisoprenoids/metabolism,pharmacology Olfactory Mucosa/cytology Phosphorylation/drug effects,physiology Prostate/cytology Prostatic Neoplasms/metabolism,pathology Receptors, Odorant/genetics,metabolism Recombinant Proteins/genetics,metabolism Signal Transduction/drug effects,physiology p38 Mitogen-Activated Protein Kinases/metabolism
Chemicals
Ligands Neoplasm Proteins Norisoprenoids OR51E2 protein, human Receptors, Odorant Recombinant Proteins beta-ionone Androsterone JNK Mitogen-Activated Protein Kinases p38 Mitogen-Activated Protein Kinases Calcium
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Neuhaus Eva M
From the Department of Cell Physiology, Ruhr-University Bochum, 44780 Bochum. Electronic address: [email protected].
Zhang Weiyi
From the Department of Cell Physiology, Ruhr-University Bochum, 44780 Bochum.
Gelis Lian
From the Department of Cell Physiology, Ruhr-University Bochum, 44780 Bochum.
Deng Ying
From the Department of Cell Physiology, Ruhr-University Bochum, 44780 Bochum.
Noldus Joachim
Department of Urology, Ruhr-University Bochum, Marienhospital Herne, 44627 Herne, Germany.
Hatt Hanns
From the Department of Cell Physiology, Ruhr-University Bochum, 44780 Bochum.
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
DOI
10.1074/jbc.M109.012096
Email
[email protected]
Published
2009-06-12
Epub
2009-00-23
Pages
16218-16225
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2713531
Subset
IM
External Links
PubMed source DOI: 10.1074/jbc.M109.012096 PMC Full Text View journal details
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