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Title: Expression and potential role of the peptide orexin-A in prostate cancer

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 suggestingmore » that orexin-A and its receptor might represent novel therapeutic targets to challenge this aggressive cancer. - Highlights: • Orexin-A and OX1 receptor are present in human cancer prostate tissues. • Orexin-A up-regulates OX1 receptor expression in LNCaP cells. • Orexin-A inhibits testosterone-induced nuclear translocation of androgen receptor.« less
Authors:
 [1] ; ;  [2] ;  [3] ;  [4] ;  [5] ; ;  [1] ;  [2] ;  [6] ;  [2] ;  [2]
  1. Department of Biology, University of Naples Federico II (Italy)
  2. Department of Veterinary Medicine and Animal Productions, University of Naples Federico II (Italy)
  3. Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II (Italy)
  4. Department of Urology, “A. Cardarelli” Hospital, Naples (Italy)
  5. Department of Pathology, “A. Cardarelli” Hospital, Naples (Italy)
  6. Institute of Genetics and Biophysics “A. Buzzati-Traverso”, CNR, Naples (Italy)
Publication Date:
OSTI Identifier:
22462246
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 464; Journal Issue: 4; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; CARCINOMAS; CENTRAL NERVOUS SYSTEM; DRUGS; GTP-ASES; HUMAN POPULATIONS; MESSENGER-RNA; METABOLIC DISEASES; PEPTIDES; PROSTATE; RECEPTORS; SIGNALS; TESTOSTERONE