title: Prostaglandin E2 Stimulates the beta-catenin/T cell factor-dependent transcription in colon cancer.
abstract: Cyclooxygenase and its derived prostaglandin E2 (PGE2) have been shown to stimulate the growth of cancer cells and promote tumor angiogenesis. Here, we show that PGE2 activated the beta-catenin/T cell factor-dependent transcription in colon cancer cells through the cAMP/protein kinase A pathway. The expression of cyclin D1 and vascular endothelial growth factor was induced by PGE2 in LS-174T cells. Moreover, PGE2 and mutated beta-catenin stimulated the transcription of cyclin D1 and vascular endothelial growth factor in a synergistic fashion. Mechanistically, PGE2 increased the phosphorylation of glycogen synthase kinase-3 and consequently accumulated beta-catenin. In addition, PGE2 induced the expression of T cell factor-4 transcription factor, which formed transcriptionally active complex with beta-catenin. In animal experiments, administration of 16,16-dimethyl PGE2 strongly increased the expression of cyclin D1 and vascular endothelial growth factor in APC(min/+) mouse polyps. Thus, our results provide a novel mechanism, suggesting that cyclooxygenase-2/PGE2 may exert pro-oncogenic actions through stimulating the beta-catenin/T cell factor-mediated transcription, which plays critical roles in colorectal carcinogenesis.
authors.affiliation: Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
authors.forename: Jinyi
authors.initials: J
authors.lastname: Shao
authors.forename: Chaeyong
authors.initials: C
authors.lastname: Jung
authors.forename: Chunming
authors.initials: C
authors.lastname: Liu
authors.forename: Hongmiao
authors.initials: H
authors.lastname: Sheng
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000473:pathology; D019938:Cyclin D1 / Q000378:metabolism; D051546:Cyclooxygenase 2; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D006801:Humans; D015151:Immunoblotting; D008156:Luciferases / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; D008565:Membrane Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D051176:beta Catenin; D051537:Hepatocyte Nuclear Factor 1; D019938:Cyclin D1; D012313:RNA; D008156:Luciferases; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D038362:Glycogen Synthase Kinase 3; D015232:Dinoprostone