Regulation of eicosanoid production and mitogenesis in rat intestinal epithelial cells by transforming growth factor-alpha and phorbol ester

J Clin Invest. 1994 Feb;93(2):493-8. doi: 10.1172/JCI116998.


Growth factors and tumor promoters have been shown to play a role in intestinal epithelial growth regulation and transformation. In this study, transforming growth factor-alpha (TGF alpha) and the tumor promoter, tetradecanoyl phorbol acetate (TPA), are shown to stimulate the production of eicosanoids by rat intestinal epithelial (RIE-1) cells in culture. A 4.5-kb mRNA, which hybridizes to the mouse cyclooxygenase-2 cDNA probe, is elevated 18-fold within 30 min after TGF alpha or TPA treatment. Stimulation of RIE-1 cells with TGF alpha leads to the increase of a protein (M(r) approximately 69,000), which binds a monospecific antibody to the mouse cyclooxygenase-2 protein. Dexamethasone markedly inhibits the increase of the 4.5-kb mRNA. Pretreatment of TGF alpha or TPA-stimulated RIE-1 cells with dexamethasone or cyclooxygenase inhibitors prevents the increase in eicosanoid production by these cells. Treatment of quiescent RIE-1 cells with TGF alpha stimulates mitogenesis. This mitogenic activity is blocked by pretreating the cells with dexamethasone or cyclooxygenase inhibitors. A mitogen-inducible cyclooxygenase gene is thus shown to be regulated by TGF alpha and TPA in rat intestinal epithelial cells. We suggest that products of an intestinal growth factor-inducible cyclooxygenase may play a role in the regulation of mitogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Division / drug effects*
  • Cell Line
  • DNA / biosynthesis
  • DNA Probes
  • Eicosanoids / biosynthesis*
  • Electron Transport Complex IV / biosynthesis
  • Enzyme Induction
  • Epithelial Cells
  • Epithelium / drug effects
  • Epithelium / metabolism
  • Gene Expression Regulation, Enzymologic / drug effects
  • Indomethacin / pharmacology
  • Intestinal Mucosa / metabolism
  • Kinetics
  • Mice
  • Microsomes / enzymology
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / metabolism
  • Rats
  • Sulindac / analogs & derivatives
  • Sulindac / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Thymidine / metabolism
  • Transfection
  • Transforming Growth Factor alpha / pharmacology*


  • DNA Probes
  • Eicosanoids
  • RNA, Messenger
  • Transforming Growth Factor alpha
  • Sulindac
  • sulindac sulfide
  • DNA
  • Prostaglandin-Endoperoxide Synthases
  • Electron Transport Complex IV
  • Tetradecanoylphorbol Acetate
  • Thymidine
  • Indomethacin