Cyclooxygenase 2: from inflammation to carcinogenesis

Novartis Found Symp. 2004:256:215-21; discussion 221-6, 259-69.

Abstract

Cyclooxygenase (COX) is the rate-limiting enzyme in the conversion of arachidonic acid to prostanoids. Two COX isoforms have been cloned, of which COX-1 is constitutively expressed, while the expression of COX-2 is low or nondetectable in most tissues, but can be readily induced in response to cell activation by cytokines, growth factors and tumour promoters. Thus, COX-1 is considered a housekeeping gene and thought to be responsible for the synthesis of prostanoids involved in cytoprotection of the stomach and for the production of the pro-aggregatory prostanoid thromboxane by the platelets. In contrast, COX-2 is an inducible, immediate-early gene, and its role has been related to inflammation, reproduction and carcinogenesis. Expression of COX-2 is elevated in a variety of human malignancies and in their precursor lesions. Furthermore, genetic deletion or pharmacological inhibition of COX-2 suppresses tumour growth in several animal models of carcinogenesis. In humans, elevated COX-2 expression is associated with poor prognosis in adenocarcinomas of the digestive tract and the breast, and a selective inhibitor of COX-2 reduced polyp burden in patients who suffer from familial adenomatous polyposis. Thus, COX-2 seems to be a relevant target in chemoprevention.

Publication types

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

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic*
  • Chemoprevention
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / therapeutic use
  • Gene Expression Regulation, Enzymologic / genetics
  • Humans
  • Inflammation / enzymology*
  • Inflammation / pathology
  • Isoenzymes / physiology*
  • Membrane Proteins
  • Neoplasms / enzymology*
  • Neoplasms / prevention & control
  • Prostaglandin-Endoperoxide Synthases / physiology*

Substances

  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Membrane Proteins
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases