Upregulation of prostaglandin E(2) by inducible microsomal prostaglandin E synthase-1 in colon cancer

PURPOSE: Prostaglandin E(2) (PGE(2)) is known to promote carcinogenesis and cancer progression in colon cancer. Enzymes involved in the metabolism of PGE(2) include cyclooxygenase (COX)-2, microsomal prostaglandin E synthase-1 (mPGES-1), and 15-prostaglandin dehydrogenase (15-PGDH). The current study aims to determine how PGE(2) is expressed by examining patients with colorectal cancer and evaluating colon cancer cells to gain insight into changes in relevant enzymes upon induction of PGE(2). METHODS: The concentration of PGE(2) was measured in tumor tissues and adjacent normal mucosal tissues of 26 patients with colon cancer. The expression of COX-1, COX-2, mPGES-1, and 15-PGDH proteins was measured. The concentration of PGE(2) in FET colon cancer cells was measured both in the initial status and after stimulation by tumor necrosis factor (TNF)-α. The expression levels of PGE(2)-related enzymes were measured as well. RESULTS: There was no significant difference in the average concentration of PGE(2), which was measured at 453.1 pg/mL in cancer tissues and 401.2 pg/mL in normal mucosa. Among PGE(2)-related enzymes, 15-PGDH was expressed at a lower level in tumor cells than in normal mucosa. In colon cancer cells, PGE(2) was found to be upregulated upon stimulation by TNF-α, which led to strong induction of mPGES-1 without any change in the expression of COX-2 among the PGE(2)-related enzymes. CONCLUSION: These results demonstrated that PGE(2) can be induced by stimuli such as TNF-α, and suggest that activation of mPGES-1 is more closely related than that of COX-2 in the induction of PGE(2) on colon cancer.