Genetic deletion of mPGES-1 accelerates intestinal tumorigenesis in APCMin/+ mice
2008 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 372, no 1, 249-253 p.Article in journal (Refereed) Published
The induced synthesis of bioactive prostanoids downstream of cyclooxygenase-2 (COX-2) and prostaglandin H2 (PGH2) exerts a critical event in colorectal carcinogenesis. Here we demonstrate that APCMin/+ mice with genetic deletion of microsomal prostaglandin E synthase-1 (mPGES-1), which catalyses the terminal conversion of PGH2 into PGE2, 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 PGE2 related enzymes (COX-1, COX-2, mPGES-2, cPGES, and 15-PGDH) or receptors (EP1-4) was obvious among the mPGES-1 deficient mice. PGE2 levels were suppressed in tumors of mPGES-1 deficient animals, but the concentrations of other PGH2 derived prostanoids were generally enhanced, being most prominent for TxA2 and PGD2. Thus, we hypothesise that a redirected synthesis towards other lipid mediators might (over)compensate for loss of mPGES-1/PGE2 during intestinal tumorigenesis. Nevertheless, our results question the suitability for mPGES-1 targeting therapy in the treatment or prevention of colorectal cancer. © 2008 Elsevier Inc. All rights reserved.
Place, publisher, year, edition, pages
2008. Vol. 372, no 1, 249-253 p.
6-Ketoprostaglandin F1 alpha/analysis Animals Cell Transformation, Neoplastic/*genetics/pathology Colorectal Neoplasms/*genetics/pathology Dinoprostone/analysis/*metabolism Female *Gene Deletion Intramolecular Oxidoreductases/*genetics Male Mice Mice, Mut
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-43256DOI: 10.1016/j.bbrc.2008.05.026Local ID: 73147OAI: oai:DiVA.org:liu-43256DiVA: diva2:264115