|
KMID : 1140220210260040304
|
|
대한암예방학회지
2021 Volume.26 No. 4 p.304 ~ p.308
|
|
|
Epithelial Cell-specific Deletion of Microsomal Prostaglandin E Synthase-1 Does Not Influence Colon Tumor Development in Mice
|
|
Nakanishi Masako
Rosenberg Daniel W.
|
|
|
Abstract
|
|
|
|
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.
|
|
|
KEYWORD
|
|
|
PGE2, mPGES-1, Colonic neoplasms, Azoxymethane, Dextran sulfate sodium
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
 
|
|