title: Expression of type 2 orexin receptor in human endometrium and its epigenetic silencing in endometrial cancer.
abstract: BACKGROUND
  Orexins A and B are neuropeptides that bind and activate 2 types of receptors. In addition to direct action in the brain, the orexinergic system has broader implications in peripheral organs, and it has been proposed to have a role in the induction of apoptosis. There are very few data on the endometrium.
  
  
  OBJECTIVE
  The expression and epigenetic regulation of type 2 orexin receptor (OX2R) was investigated in the human endometrium as well as in endometrial endometrioid carcinoma (EEC).
  
  
  METHODS
  OX2R localization was studied by immunohistochemistry in normal endometrium (n = 24) and in EEC (n = 32). The DNA methylation status of a CpG island located in the first exon of OX2R was analyzed by bisulfite sequencing in normal (n = 18), EEC (n = 34), and 3 endometrial cell lines. On the latter, mRNA expression and Western blotting as well as in vitro induction with orexin were performed.
  
  
  RESULTS
  Expression of the OX2R protein was detected in normal endometrial epithelia, whereas it was frequently lacking in EEC. This loss was associated with hypermethylation of OX2R in EEC in comparison with normal endometrium (median CpG methylation percentages of 48.85% and 5.85%, respectively). In cell lines, hypermethylation correlated with weak OX2R expression. Additionally, in vitro treatment of the 3 EEC cell lines with orexins A and B did not result in proliferation change
  
  
  CONCLUSIONS
  Altogether our data provide evidence for the epigenetic silencing of OX2R in EEC. The implication of the OX2R loss in tumoral progression remains to be elucidated.
authors.affiliation: Department of Experimental Pathology, University of Liège, Tour de Pathologie (B23 + 4), Boulevard de l'Hôpital 1, B 4000 Liege Belgium. pierre.dehan@ulg.ac.be
authors.forename: P
authors.initials: P
authors.lastname: Dehan
authors.forename: C
authors.initials: C
authors.lastname: Canon
authors.forename: G
authors.initials: G
authors.lastname: Trooskens
authors.forename: M
authors.initials: M
authors.lastname: Rehli
authors.forename: C
authors.initials: C
authors.lastname: Munaut
authors.forename: W
authors.initials: W
authors.lastname: Van Criekinge
authors.forename: P
authors.initials: P
authors.lastname: Delvenne
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D044127:Epigenesis, Genetic / Q000502:physiology; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D064446:Orexin Receptors; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000235:genetics* / Q000378:metabolism; D054928:Validation Studies as Topic
chemical_list: C578626:HCRTR2 protein, human; D064446:Orexin Receptors; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide