Cyclooxygenase and its derived prostaglandin E2 (PGE 2) have been shown to stimulate the growth of cancer cells and promote tumor angiogenesis. Here, we show that PGE2 activated the β-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 β-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 β-catenin. In addition, PGE2 induced the expression of T cell factor-4 transcription factor, which formed transcriptionally active complex with β-catenin. In animal experiments, administration of 16,16-dimethyl PGE2 strongly increased the expression of cyclin D1 and vascular endothelial growth factor in APCmin/+ mouse polyps. Thus, our results provide a novel mechanism, suggesting that cyclooxygenase-2/PGE2 may exert pro-oncogenic actions through stimulating the β-catenin/T cell factor-mediated transcription, which plays critical roles in colorectal carcinogenesis.
|Number of pages||8|
|Journal||Journal of Biological Chemistry|
|State||Published - Jul 15 2005|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology