Prostaglandin EP2 receptor expression is increased in Barrett’s oesophagus and oesophageal adenocarcinoma

• Published in: Alimentary pharmacology & therapeutics 2010-02, Vol.31 (3), p.440-451
• Main Authors: JIMÉNEZ, P., PIAZUELO, E., CEBRIAN, C., ORTEGO, J., STRUNK, M., GARCÍA‐GONZALEZ, M. A., SANTANDER, S., ALCEDO, J., LANAS, A.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - pathology; Barrett Esophagus - genetics; Barrett Esophagus - pathology; Cell Line, Tumor; Cyclooxygenase 1 - metabolism; Esophageal Neoplasms - genetics; Esophageal Neoplasms - pathology; Humans; Immunohistochemistry; Precancerous Conditions; Receptors, Prostaglandin E - genetics; Receptors, Prostaglandin E - metabolism; Receptors, Prostaglandin E, EP2 Subtype; RNA, Messenger - metabolism
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/j.1365-2036.2009.04172.x

Aliment Pharmacol Ther 31, 440–451 Summary Background  Accumulating evidence suggests that cyclooxygenase‐2 (COX‐2)‐derived prostaglandin E2 (PGE2) is involved in oesophageal adenocarcinogenesis. PGE2 exerts its biological action by binding to specific receptors (EP1, EP2, EP3 and EP4). Aim  To investigate which PGE2 receptor subtypes regulate PGE2 signals in the oesophageal adenocarcinoma sequence. Methods  Expression was determined in oesophageal biopsies from 85 patients with oesophagitis, Barrett’s metaplasia, intraepithelial neoplasia, oesophageal adenocarcinoma and normal oesophagus. Levels of mRNA and protein expression were determined by quantitative PCR, immunohistochemistry and western‐blot. Expression of EP receptors was also determined in response to acid and bile exposure in the Barrett’s adenocarcinoma cell line OE33. Results  All four EP receptors subtypes were expressed in human oesophageal tissues. COX‐2 and, especially, EP2 were increased in the Barrett’s metaplasia‐intraepithelial neoplasia‐adenocarcinoma sequence. Expression of the EP4 receptor protein was increased in oesophageal adenocarcinoma. In contrast, expression levels of COX‐1 and EP3 receptor were decreased along the sequence. No differences in EP1 expression were found. Treatment with the bile acid deoxycholate increased COX‐2, EP1, EP2 and EP4 expression in OE33 cells. Conclusions  Our data suggest that in addition to COX‐2, EP2 and EP4 receptors could be a selective target in the prevention and/or treatment of the Barrett’s‐associated adenocarcinoma.