title: The orexin type 1 receptor is overexpressed in advanced prostate cancer with a neuroendocrine differentiation, and mediates apoptosis.
abstract: OBJECTIVE
  In the present study, we have examined the presence of orexins and their receptors in prostate cancer (CaP) and investigated their effects on the apoptosis of prostate cancer cells.
  
  
  METHODS
  We have localised the orexin type 1 and 2 receptors (OX1R and OX2R) and orexin A (OxA) in CaP sections of various grades and we have quantified tumour cells containing OX1R. Expression of OX1R was evaluated in the androgeno-dependent (AD) LNCaP and the androgeno-independent (AI) DU145 prostate cancer cells submitted or not to a neuroendocrine differentiation. The effects of orexins on the apoptosis and viability of DU145 cells were also investigated.
  
  
  RESULTS
  OX1R is strongly expressed in carcinomatous foci exhibiting a neuroendocrine differentiation, and the number of OX1R-stained cancer cells increases with the grade of the CaP. In contrast, OX2R is only detected in scattered malignant cells in high grade CaP. OX1R is expressed in the AI DU145 cells but is undetectable in the LNCaP cells. Acquisition of a neuroendocrine phenotype by the DU145 cells is associated with an overexpression of OX1R. Orexins induce the apoptosis of DU145 cells submitted to a neuroendocrine differentiation.
  
  
  CONCLUSIONS
  The present data indicate that OX1R-driven apoptosis is overexpressed in AI CaP exhibiting a neuroendocrine differentiation opening a gate for novel therapies for these aggressive cancers which are incurable until now.
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Biomedical Research and Innovation Institute (IRIB), University of Rouen, Mont-Saint-Aignan, France.
authors.forename: David
authors.initials: D
authors.lastname: Alexandre
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Biomedical Research and Innovation Institute (IRIB), University of Rouen, Mont-Saint-Aignan, France.
authors.forename: Coralie
authors.initials: C
authors.lastname: Hautot
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Biomedical Research and Innovation Institute (IRIB), University of Rouen, Mont-Saint-Aignan, France.
authors.forename: Marwa
authors.initials: M
authors.lastname: Mehio
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Biomedical Research and Innovation Institute (IRIB), University of Rouen, Mont-Saint-Aignan, France.
authors.forename: Lydie
authors.initials: L
authors.lastname: Jeandel
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Biomedical Research and Innovation Institute (IRIB), University of Rouen, Mont-Saint-Aignan, France.
authors.forename: Maïté
authors.initials: M
authors.lastname: Courel
authors.affiliation: University Paris-Diderot, Sorbonne Paris Cité, CRB3, Centre de Recherche Biomédicale Bichat Beaujon (CRB3), UMR773, INSERM, F-75018 Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Voisin
authors.affiliation: University Paris-Diderot, Sorbonne Paris Cité, CRB3, Centre de Recherche Biomédicale Bichat Beaujon (CRB3), UMR773, INSERM, F-75018 Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Couvineau
authors.affiliation: Department of Pathology, University Hospital of Rouen, Institute for Biomedical Research, University of Rouen, Rouen, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Gobet
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Biomedical Research and Innovation Institute (IRIB), University of Rouen, Mont-Saint-Aignan, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Leprince
authors.affiliation: Department of Urology, University Hospital of Rouen, Institute for Biomedical Research, University of Rouen, Rouen, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Pfister
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Biomedical Research and Innovation Institute (IRIB), University of Rouen, Mont-Saint-Aignan, France.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Anouar
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Biomedical Research and Innovation Institute (IRIB), University of Rouen, Mont-Saint-Aignan, France. Electronic address: nicolas.chartrel@univ-rouen.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chartrel
mesh_terms: D017209:Apoptosis / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D055099:Neuroendocrine Cells / Q000378:metabolism / Q000473:pathology; D064446:Orexin Receptors / Q000235:genetics / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D064446:Orexin Receptors; D012333:RNA, Messenger
keywords: Apoptosis; Cancer; G protein-coupled receptor; Neuroendocrine differentiation; Neuropeptide; Proliferation; Prostate cancer therapy