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

Jinyi Shao, Chaeyong Jung, Chunming Liu, Hongmiao Sheng

Research output: Contribution to journalArticlepeer-review

189 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)26565-26572
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number28
DOIs
StatePublished - Jul 15 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Prostaglandin E2 stimulates the β-catenin/T cell factor-dependent transcription in colon cancer'. Together they form a unique fingerprint.

Cite this