Cloning and characterization of a growth factor-inducible cyclooxygenase gene from rat intestinal epithelial cells

Am J Physiol. 1994 May;266(5 Pt 1):G822-7. doi: 10.1152/ajpgi.1994.266.5.G822.


Growth factors have been shown to play a role in intestinal epithelial growth regulation and transformation. Utilizing standard differential cloning techniques, we have isolated a growth factor-inducible gene (RS-2) from rat intestinal epithelial cells that has approximately 95% homology to the mouse mitogen-inducible cyclooxygenase (COX-2) at the amino acid level. This cDNA hybridizes to a approximately 4.5-kb mRNA from transforming growth factor (TGF)-alpha-stimulated rat intestinal epithelial (RIE-1) cells and is constitutively expressed in vivo in adult rat kidney and brain. Nuclear run-on experiments demonstrate that the increase of RS-2 mRNA after TGF-alpha stimulation is in part due to an increased transcription rate of the gene. The coding region for RS-2 was subcloned into a pCMV-2 expression vector, and the RS-2 protein was expressed in COS-1 cells. Microsomal fractions isolated from the COS-1 cells transfected with the RS-2 expression vector contained cyclooxygenase activity. In addition to the production of prostaglandins, the recombinant RS-2 protein also catalyzed the formation of three other eicosanoid products. In summary, we have cloned a mitogen-inducible cyclooxygenase gene from rat intestinal cells that is induced following growth factor stimulation.

Publication types

  • Comparative Study
  • 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

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Northern
  • Brain / enzymology
  • Cell Line
  • Cell Nucleus / metabolism
  • Chlorocebus aethiops
  • Cloning, Molecular
  • DNA, Complementary / analysis
  • Enzyme Induction
  • Epithelium / drug effects
  • Epithelium / enzymology
  • Gene Expression Regulation, Enzymologic* / drug effects
  • Gene Library
  • Intestines
  • Kidney / enzymology
  • Mice
  • Microsomes / enzymology
  • Molecular Sequence Data
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • RNA, Messenger / biosynthesis*
  • RNA, Messenger / metabolism
  • Rats
  • Sequence Homology, Amino Acid
  • Transfection
  • Transforming Growth Factor alpha / pharmacology*


  • DNA, Complementary
  • RNA, Messenger
  • Transforming Growth Factor alpha
  • Prostaglandin-Endoperoxide Synthases