title: Activation of an olfactory receptor inhibits proliferation of prostate cancer cells.
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.
authors.affiliation: From the Department of Cell Physiology, Ruhr-University Bochum, 44780 Bochum. Electronic address: eva.neuhaus@rub.de.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Neuhaus
authors.affiliation: From the Department of Cell Physiology, Ruhr-University Bochum, 44780 Bochum.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Zhang
authors.affiliation: From the Department of Cell Physiology, Ruhr-University Bochum, 44780 Bochum.
authors.forename: Lian
authors.initials: L
authors.lastname: Gelis
authors.affiliation: From the Department of Cell Physiology, Ruhr-University Bochum, 44780 Bochum.
authors.forename: Ying
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Urology, Ruhr-University Bochum, Marienhospital Herne, 44627 Herne, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Noldus
authors.affiliation: From the Department of Cell Physiology, Ruhr-University Bochum, 44780 Bochum.
authors.forename: Hanns
authors.initials: H
authors.lastname: Hatt
mesh_terms: D000738:Androsterone / Q000378:metabolism* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007668:Kidney / Q000166:cytology; D008024:Ligands; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D045792:Norisoprenoids / Q000378:metabolism / Q000494:pharmacology; D009831:Olfactory Mucosa / Q000166:cytology; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D011467:Prostate / Q000166:cytology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D018035:Receptors, Odorant / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D008024:Ligands; D009363:Neoplasm Proteins; D045792:Norisoprenoids; C417566:OR51E2 protein, human; D018035:Receptors, Odorant; D011994:Recombinant Proteins; C008157:beta-ionone; D000738:Androsterone; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium