15-ketoprostaglandin-e2 and Bile-Duct-Neoplasms

15-ketoprostaglandin-e2 has been researched along with Bile-Duct-Neoplasms* in 1 studies

Other Studies

1 other study(ies) available for 15-ketoprostaglandin-e2 and Bile-Duct-Neoplasms

ArticleYear
15-hydroxyprostaglandin dehydrogenase-derived 15-keto-prostaglandin E2 inhibits cholangiocarcinoma cell growth through interaction with peroxisome proliferator-activated receptor-γ, SMAD2/3, and TAP63 proteins.
    The Journal of biological chemistry, 2013, Jul-05, Volume: 288, Issue:27

    Prostaglandin E2 (PGE2) is a potent lipid mediator that plays a key role in inflammation and carcinogenesis. NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the oxidation of the 15(S)-hydroxyl group of PGE2, which leads to PGE2 biotransformation. In this study, we showed that the 15-PGDH-derived 15-keto-PGE2 is an endogenous peroxisome proliferator-activated receptor-γ (PPAR-γ) ligand that causes PPAR-γ dissociation from Smad2/3, allowing Smad2/3 association with the TGF-β receptor I and Smad anchor for receptor activation and subsequent Smad2/3 phosphorylation and transcription activation in human cholangiocarcinoma cells. The 15-PGDH/15-keto-PGE2-induced Smad2/3 phosphorylation resulted in the formation of the pSmad2/3-TAP63-p53 ternary complex and their binding to the TAP63 promoter, inducing TAP63 autotranscription. The role of TAP63 in 15-PGDH/15-keto-PGE2-induced inhibition of tumor growth was further supported by the observation that knockdown of TAP63 prevented 15-PGDH-induced inhibition of tumor cell proliferation, colony formation, and migration. These findings disclose a novel 15-PGDH-mediated 15-keto-PGE2 signaling cascade that interacts with PPAR-γ, Smad2/3, and TAP63.

    Topics: Animals; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cell Line, Tumor; Cell Proliferation; Cholangiocarcinoma; Dinoprostone; Humans; Hydroxyprostaglandin Dehydrogenases; Male; Mice; Mice, Inbred NOD; Mice, SCID; Phosphorylation; PPAR gamma; Receptors, Transforming Growth Factor beta; Signal Transduction; Smad2 Protein; Smad3 Protein; Transcription Factors; Transcription, Genetic; Tumor Suppressor Protein p53; Tumor Suppressor Proteins

2013
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