Prostaglandin E2 stimulates the β-catenin/T cell factor-dependent transcription in colon cancer

被引:164
作者
Shao, JY
Jung, CY
Liu, CM
Sheng, HM [1 ]
机构
[1] Indiana Univ, Sch Med, Dept Surg, Indianapolis, IN 46202 USA
[2] Indiana Univ, Sch Med, Dept Urol, Indianapolis, IN 46202 USA
[3] Indiana Univ, Sch Med, Ctr Canc, Indianapolis, IN 46202 USA
[4] Univ Texas, Med Branch, Dept Human Biol Chem & Genet, Galveston, TX 77555 USA
关键词
D O I
10.1074/jbc.M413056200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cyclooxygenase and its derived prostaglandin E-2 (PGE(2)) 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 PGE(2) in LS-174T cells. Moreover, PGE(2) and mutated beta-catenin stimulated the transcription of cyclin D1 and vascular endothelial growth factor in a synergistic fashion. Mechanistically, PGE(2) increased the phosphorylation of glycogen synthase kinase-3 and consequently accumulated beta-catenin. In addition, PGE(2) 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 PGE(2) 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/PGE(2) may exert pro-oncogenic actions through stimulating the beta-catenin/T cell factor-mediated transcription, which plays critical roles in colorectal carcinogenesis.
引用
收藏
页码:26565 / 26572
页数:8
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