15-Hydroxyprostaglandin dehydrogenase as a marker in colon carcinogenesis: analysis of the prostaglandin pathway in human colonic tissue

ABSTRACT

BACKGROUND/AIMS: Cyclooxygenase-2 (COX-2), 15-hydroxyprostaglandin dehydrogenase (15-PGDH), and microsomal prostaglandin E synthase-1 (mPGEs-1) regulate prostaglandin E₂ (PGE₂) expression and are involved in colon carcinogenesis. We investigated the expression of PGE₂ and its regulating genes in sporadic human colon tumors and matched normal tissues. METHODS: Twenty colonic adenomas and 27 colonic adenocarcinomas were evaluated. COX-2 and 15-PGDH expression was quantified by real-time polymerase chain reaction. The expression of PGE₂ and mPGEs-1 was measured using enzyme-linked immunosorbent assay and Western blotting, respectively. RESULTS: The expression of COX-2, mPGEs-1, and PGE₂ did not differ between the adenomas and matched distant normal tissues. 15-PGDH expression was lower in adenomas than in the matched normal colonic tissues (P<0.001). In adenocarcinomas, mPGEs-1 and PGE₂ expression was significantly higher (P<0.001 and P=0.020, respectively), and COX-2 expression did not differ from that in normal tissues (P=0.207). 15-PGDH expression was significantly lower in the normal colonic mucosa from adenocarcinoma patients than in the normal mucosa from adenoma patients (P=0.018). CONCLUSIONS: Early inactivation of 15-PGDH, followed by activation of COX-2 and mPGEs-1, contributes to PGE₂ production, leading to colon carcinogenesis. 15-PGDH might be a novel candidate marker for early detection of field defects in colon carcinogenesis.