Acceleration of intestinal polyposis through prostaglandin receptor EP2 in Apc(Delta 716) knockout mice.
Nat Med
; 7(9): 1048-51, 2001 Sep.
Article
en En
| MEDLINE
| ID: mdl-11533709
ABSTRACT
Arachidonic acid is metabolized to prostaglandin H(2) (PGH(2)) by cyclooxygenase (COX). COX-2, the inducible COX isozyme, has a key role in intestinal polyposis. Among the metabolites of PGH(2), PGE(2) is implicated in tumorigenesis because its level is markedly elevated in tissues of intestinal adenoma and colon cancer. Here we show that homozygous deletion of the gene encoding a cell-surface receptor of PGE(2), EP2, causes decreases in number and size of intestinal polyps in Apc(Delta 716) mice (a mouse model for human familial adenomatous polyposis). This effect is similar to that of COX-2 gene disruption. We also show that COX-2 expression is boosted by PGE(2) through the EP2 receptor via a positive feedback loop. Homozygous gene knockout for other PGE(2) receptors, EP1 or EP3, did not affect intestinal polyp formation in Apc(Delta 716) mice. We conclude that EP2 is the major receptor mediating the PGE2 signal generated by COX-2 upregulation in intestinal polyposis, and that increased cellular cAMP stimulates expression of more COX-2 and vascular endothelial growth factor in the polyp stroma.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Prostaglandina-Endoperóxido Sintasas
/
Receptores de Prostaglandina E
/
Poliposis Adenomatosa del Colon
/
Isoenzimas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Nat Med
Asunto de la revista:
BIOLOGIA MOLECULAR
/
MEDICINA
Año:
2001
Tipo del documento:
Article
País de afiliación:
Japón