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

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 spo...

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Main Authors: Dong-Hoon Yang, Yeon-Mi Ryu, Sun-Mi Lee, Jin-Yong Jeong, Soon Man Yoon, Byong Duk Ye, Jeong-Sik Byeon, Suk-Kyun Yang, Seung-Jae Myung
Format: Article
Language:English
Published: Korean Association for the Study of Intestinal Diseases 2017-01-01
Series:Intestinal Research
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Online Access:https://doi.org/10.5217/ir.2017.15.1.75
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Summary: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.
ISSN:1598-9100