Article (Scientific journals)
Expression of type 2 orexin receptor in human endometrium and its epigenetic silencing in endometrial cancer.
Dehan, Pierre; Canon, C.; Trooskens, G. et al.
2013In Journal of Clinical Endocrinology and Metabolism, 98 (4), p. 1549-57
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Abstract :
[en] CONTEXT: 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.
Disciplines :
Oncology
Author, co-author :
Dehan, Pierre ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Canon, C.
Trooskens, G.
Rehli, M.
Munaut, Carine  ;  Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Van Criekinge, W.
Delvenne, Philippe ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Language :
English
Title :
Expression of type 2 orexin receptor in human endometrium and its epigenetic silencing in endometrial cancer.
Publication date :
2013
Journal title :
Journal of Clinical Endocrinology and Metabolism
ISSN :
0021-972X
eISSN :
1945-7197
Publisher :
Oxford University Press, New York, United States - New York
Volume :
98
Issue :
4
Pages :
1549-57
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 23 May 2013

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