| First Author | Elander N | Year | 2008 |
| Journal | Biochem Biophys Res Commun | Volume | 372 |
| Issue | 1 | Pages | 249-53 |
| PubMed ID | 18485889 | Mgi Jnum | J:136951 |
| Mgi Id | MGI:3797426 | Doi | 10.1016/j.bbrc.2008.05.026 |
| Citation | Elander N, et al. (2008) Genetic deletion of mPGES-1 accelerates intestinal tumorigenesis in APC(Min/+) mice. Biochem Biophys Res Commun 372(1):249-53 |
| abstractText | The induced synthesis of bioactive prostanoids downstream of cyclooxygenase-2 (COX-2) and prostaglandin H(2) (PGH(2)) exerts a critical event in colorectal carcinogenesis. Here we demonstrate that APC(Min/+) mice with genetic deletion of microsomal prostaglandin E synthase-1 (mPGES-1), which catalyses the terminal conversion of PGH(2) into PGE(2), surprisingly develop more and generally larger intestinal tumors than do mPGES-1 wild type littermates (mean number of tumors/intestine 80 vs. 38, p<0.0005, mean tumor diameter 1.64 vs. 1.12 mm, p<0.0005). No deviation regarding the expression of other PGE(2) related enzymes (COX-1, COX-2, mPGES-2, cPGES, and 15-PGDH) or receptors (EP1-4) was obvious among the mPGES-1 deficient mice. PGE(2) levels were suppressed in tumors of mPGES-1 deficient animals, but the concentrations of other PGH(2) derived prostanoids were generally enhanced, being most prominent for TxA(2) and PGD(2). Thus, we hypothesise that a redirected synthesis towards other lipid mediators might (over)compensate for loss of mPGES-1/PGE(2) during intestinal tumorigenesis. Nevertheless, our results question the suitability for mPGES-1 targeting therapy in the treatment or prevention of colorectal cancer. |
