The role of cyclooxygenases in inflammation, cancer, and development

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

    Research output: Contribution to journalReview articlepeer-review

    1172 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

    Keywords

    • Cancer
    • Cyclooxygenase
    • Development
    • Inflammation

    ASJC Scopus subject areas

    • Molecular Biology
    • Genetics
    • Cancer Research

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