The role of cyclooxygenases in inflammation, cancer, and development

Christopher S. Williams, Moss Mann, Raymond N. DuBois

Research output: Contribution to journalReview article

1135 Scopus citations

Abstract

The cyclooxygenase (COX) enzymes catalyze a key step in the conversion of arachidonate to PGH2, the immediate substrate for a series of cell specific prostaglandin and thromboxane synthases. Prostaglandins play critical roles in numerous biologic processes, including the regulation of immune function, kidney development, reproductive biology, and gastrointestinal integrity. There are two COX isoforms, which differ mainly in their pattern of expression. COX-1 is expressed in most tissues, whereas COX-2 usually is absent, but is induced by numerous physiologic stimuli. Surprisingly, disruption of Cox1 (Ptgs1) in the mouse did not result in gastrointestinal abnormalities. cox-2 (Ptgs2) null mice show reproductive anomalies and defects in kidney development. Epidemiologic, animal, and human data indicate that NSAIDs, inhibitors of cyclooxygenase, are chemopreventive for colon cancer. COX-2 is overexpressed in 50 of benign polyps and 80-85 of adenocarcinomas. Offspring from cox-2 null by Apc(Δ716) matings exhibit an 86 reduction in polyp number when compared to offspring from control animals, thus providing genetic evidence that COX-2 contributes to tumor formation or growth. The in vivo mechanism by which COX-2 affects tumor growth has not been determined. It is possible that both tumor and stromally derived COX-2 could influence tumor angiogenesis and/or immune function.

Original languageEnglish (US)
Pages (from-to)7908-7916
Number of pages9
JournalOncogene
Volume18
Issue number55
DOIs
StatePublished - Dec 20 1999

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Keywords

  • Cancer
  • Cyclooxygenase
  • Development
  • Inflammation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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