RGD Reference Report - Characterization of the Prostaglandin E2 path way in a Rat Model of Esophageal Adenocarcinoma. - Rat Genome Database

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Characterization of the Prostaglandin E2 path way in a Rat Model of Esophageal Adenocarcinoma.

Authors: Piazuelo, E  Santander, S  Cebrian, C  Jimenez, P  Pastor, C  Garcia-Gonzalez, MA  Esteva, F  Esquivias, P  Ortego, J  Lanas, A 
Citation: Piazuelo E, etal., Curr Cancer Drug Targets. 2011 Oct 27.
RGD ID: 5687745
Pubmed: PMID:22165968   (View Abstract at PubMed)

Accumulating evidence indicates that the cyclooxygenase-2 (COX-2)/prostaglandin E(2) (PGE(2)) pathway plays a key role in esophageal carcinogenesis. A better understanding of the pathway downstream of COX-2 may reveal novel targets for the prevention of esophageal adenocarcinoma (EAC). The objective of this study was to characterize the profile of genes involved in PGE(2) metabolism and signaling in an experimental model of EAC. Esophagojejunostomy with gastric preservation was performed in wistar rats to induce gastroduodenal reflux. Rats were sacrificed 2 or 4 months after surgery. Nine non-operated rats were used to obtain normal (control) esophageal tissues. RESULTS: All rats that underwent esophagojejunostomy developed inflammation. In addition, 90% of the animals showed intestinal metaplasia; of those, 40% progressed to AC. This process was accompanied by a significant increase in esophageal PGE(2)levels and the induction of both mRNA and protein levels of COX-2, COX-1, prostaglandin E synthase, 15-hydroxyprostaglandin dehydrogenase, and PGE(2) receptors EP3, EP4 and especially EP2, which rose to particularly high levels in experimental rats. In addition, exposure to a selective COX-2 inhibitor (SC58125) or an EP1/EP2 antagonist (AH6809), but not an EP4 antagonist (AH23848B), significantly reduced cell proliferation of esophageal explants in 24 hour-organ culture experiments. Our data suggest that, in addition to COX-2, other components of the PGE2 pathway, including COX-1, may play important roles in the development of EAC induced by gastroduodenal reflux in the rat. Although it must be confirmed in vivo, the EP2 receptor may represent a promising selective target in the prevention of Barrett's associated AC.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Esophageal Neoplasms  ISOPtgs2 (Rattus norvegicus)5687745; 5687745mRNA and protein:increased expression:EsophagusRGD 
Esophageal Neoplasms  IEP 5687745mRNA and protein:increased expression:EsophagusRGD 
esophagus adenocarcinoma  ISOPtgs1 (Rattus norvegicus)5687745; 5687745mRNA and protein:increased expression:EsophagusRGD 
esophagus adenocarcinoma  IEP 5687745mRNA and protein:increased expression:EsophagusRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of cell population proliferation  IMP 5687745 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptgs1  (prostaglandin-endoperoxide synthase 1)
Ptgs2  (prostaglandin-endoperoxide synthase 2)

Genes (Mus musculus)
Ptgs1  (prostaglandin-endoperoxide synthase 1)
Ptgs2  (prostaglandin-endoperoxide synthase 2)

Genes (Homo sapiens)
PTGS1  (prostaglandin-endoperoxide synthase 1)
PTGS2  (prostaglandin-endoperoxide synthase 2)


Additional Information