title: Expression and potential role of the peptide orexin-A in prostate cancer.
abstract: The peptides orexin-A and orexin-B and their G protein-coupled OX1 and OX2 receptors are involved in multiple physiological processes in the central nervous system and peripheral organs. Altered expression or signaling dysregulation of orexins and their receptors have been associated with a wide range of human diseases including narcolepsy, obesity, drug addiction, and cancer. Although orexin-A, its precursor molecule prepro-orexin and OX1 receptor have been detected in the human normal and hyperplastic prostate tissues, their expression and function in the prostate cancer (PCa) remains to be addressed. Here, we demonstrate for the first time the immunohistochemical localization of orexin-A in human PCa specimens, and the expression of prepro-orexin and OX1 receptor at both protein and mRNA levels in these tissues. Orexin-A administration to the human androgen-dependent prostate carcinoma cells LNCaP up-regulates OX1 receptor expression resulting in a decrease of cell survival. Noteworthy, nanomolar concentrations of the peptide counteract the testosterone-induced nuclear translocation of the androgen receptor in the cells: the orexin-A action is prevented by the addition of the OX1 receptor antagonist SB-408124 to the test system. These findings indicate that orexin-A/OX1 receptor interaction interferes with the activity of the androgen receptor which regulates PCa onset and progression, thus suggesting that orexin-A and its receptor might represent novel therapeutic targets to challenge this aggressive cancer.
authors.affiliation: Department of Biology, University of Naples Federico II, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Valiante
authors.affiliation: Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Liguori
authors.affiliation: Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Tafuri
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Italy.
authors.forename: Luigi Michele
authors.initials: LM
authors.lastname: Pavone
authors.affiliation: Department of Urology, "A. Cardarelli" Hospital, Naples, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Campese
authors.affiliation: Department of Pathology, "A. Cardarelli" Hospital, Naples, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Monaco
authors.affiliation: Department of Biology, University of Naples Federico II, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Iachetta
authors.affiliation: Department of Biology, University of Naples Federico II, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Assisi
authors.affiliation: Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Mirabella
authors.affiliation: Institute of Genetics and Biophysics "A. Buzzati-Traverso", CNR, Naples, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Forte
authors.affiliation: Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Costagliola
authors.affiliation: Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Italy. Electronic address: avittori@unina.it.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Vittoria
mesh_terms: D021581:Active Transport, Cell Nucleus; D000368:Aged; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D064446:Orexin Receptors / Q000378:metabolism*; D000068797:Orexins / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D064446:Orexin Receptors; D000068797:Orexins; D011944:Receptors, Androgen; D013739:Testosterone
keywords: Androgen receptor translocation; Cell survival; LNCaP cells; Orexin-A; Prostate cancer; Receptor 1 for orexin