Prostaglandin EP2 receptor expression is increased in Barrett's oesophagus and oesophageal adenocarcinoma.
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).


OBJECTIVE
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.
CIBER Enfermedades Hepáticas y Digestivas (CIBERehd), University Hospital, Zaragoza, Spain. pilarj@unizar.es
P
P
Jiménez
E
E
Piazuelo
C
C
Cebrian
J
J
Ortego
M
M
Strunk
M A
MA
García-Gonzalez
S
S
Santander
J
J
Alcedo
A
A
Lanas
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D001471:Barrett Esophagus / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D011230:Precancerous Conditions; D012333:RNA, Messenger / Q000378:metabolism*; D018078:Receptors, Prostaglandin E / Q000235:genetics / Q000378:metabolism*; D058307:Receptors, Prostaglandin E, EP2 Subtype
C545644:PTGER2 protein, human; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D051545:Cyclooxygenase 1