Prostaglandin E(2) stimulates progression-related gene expression in early colorectal adenoma cells

Br J Cancer. 2006 Jun 5;94(11):1718-25. doi: 10.1038/sj.bjc.6603146.


Upregulation of cyclooxygenase-2 (COX-2) and prostaglandin-dependent vascularisation in small adenomatous polyps is an essential part of colon carcinogenesis. To study the underlying cellular mechanisms, LT97 and Caco2 human colorectal tumour cells not expressing endogenous COX-2 were exposed to 1 microM prostaglandin E(2) (PGE(2)) in their medium. At 30 min after addition, expression of c-fos was stimulated 5-fold and 1.3-fold, respectively, depending on the activation of both extracellular signal-regulated kinase and p38. The amount of c-jun in nuclear extracts was increased 20% in LT97 cells. Expression of COX-2 was upregulated 1.7-fold in LT97 cells and 1.5-fold in Caco2 2 h after prostaglandin (PG) addition by a p38-mediated pathway. The known PGE(2) target gene vascular endothelial growth factor (VEGF) was not modulated. Effects of sustained PGE(2) production were studied in VACO235 cells that have high endogenous COX-2 and in LT97 cells infected with an adenovirus expressing COX-2. Prostaglandin E(2) secretion into the medium was 1-2 nM and 250 pM, respectively. Expression of both VEGF and c-fos was high in VACO235 cells. In LT97 cells, COX-2 upregulated c-fos expression and c-jun content in nuclear extracts 1.7- and 1.2-fold, respectively, in a PG-dependent way. This shows that exogenous PGE(2) as well as COX-2 overexpression affect signalling and gene expression in a way that enhances tumour progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / genetics*
  • Cell Line, Tumor
  • Colonic Neoplasms / genetics*
  • Colorectal Neoplasms / genetics
  • Cyclooxygenase 2 / genetics
  • DNA Primers
  • Dinoprostone / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Polymerase Chain Reaction
  • Prostaglandins / metabolism
  • Proto-Oncogene Proteins c-jun / metabolism
  • Signal Transduction


  • DNA Primers
  • Prostaglandins
  • Proto-Oncogene Proteins c-jun
  • Cyclooxygenase 2
  • Dinoprostone