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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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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 un derstand 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 car bonic 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 stud ies 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.
Key Words PGE2, mPGES-1, Colonic neoplasms, Azoxymethane, Dextran sulfate sodium
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참고문헌 (20)
참고문헌 신청
Nakanishi M / 2013 / Multifaceted roles of PGE2 in inflammation and cancer / Semin Immunopathol 35:123~137
Smalley WE / 1997 / Colorectal cancer and nonsteroidal anti-inflammatory drugs / Adv Pharmacol 39:1~20
Wang D / 2013 / The role of anti-inflammatory drugs in colorectal cancer / Annu Rev Med 64:131~144
Nakanishi M / 2011 / Selective PGE(2)suppression inhibits colon carcinogenesis and modifies local mucosal immunity / Cancer Prev Res(Phila) 4:1198~1208
Nakanishi M / 2008 / Genetic deletion of mPGES-1 suppresses intestinal tumorigenesis / Cancer Res 68:3251~3259
Smalley WE / 1997 / Colorectal cancer and nonsteroidal anti-inflammatory drugs / Adv Pharmacol 39:1~20
Wang D / 2013 / The role of anti-inflammatory drugs in colorectal cancer / Annu Rev Med 64:131~144
Nakanishi M / 2011 / Selective PGE(2)suppression inhibits colon carcinogenesis and modifies local mucosal immunity / Cancer Prev Res(Phila) 4:1198~1208
Nakanishi M / 2008 / Genetic deletion of mPGES-1 suppresses intestinal tumorigenesis / Cancer Res 68:3251~3259
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