Activation of the COX-2/microsomal
prostaglandin E synthase-1 (mPGES-1)/
prostaglandin E2 (
PGE2) signaling axis is a hallmark of many
cancers, including
colorectal cancer, prompting the implementation of prevention strategies targeting COX-2 activity. We have previously shown that targeting the downstream terminal
PGE2 synthase, mPGES-1 (Ptges), specifically reduces inducible
PGE2 formation without disrupting synthesis of other essential
prostanoids, thereby conferring dramatic
cancer protection against colon
carcinogenesis in multiple mouse models. In order to accelerate its development as a viable drug target, and to better understand the mechanisms by which
PGE2 influences colon
carcinogenesis, we recently developed a conditional Ptges knockout mouse model (cKO). To evaluate the functional role of Ptges directly within the colonic epithelia, cKO mice were crossed with
carbonic anhydrase 1 (Car1)-Cre mice (cKO.Car1), and colon
tumors were induced using the
azoxymethane/
dextran sodium sulfate protocol. Unexpectedly, epithelial-specific blockade of Ptges failed to protect mice against colon
tumor development. Further studies using the cKO mouse model will be necessary to pinpoint the cell type-specific location of mPGES-1 and its control of inducible
PGE2 formation that drives
tumor formation in the colon.