The role of COX-2 in intestinal cancer

Christopher Williams, Rebecca L. Shattuck-Brandt, Raymond N. DuBois

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Abstract

Cyclooxygenase (COX), the key regulatory enzyme for prostaglandin synthesis is transcribed from two distinct genes. COX-1 is expressed constitutively in most tissues, and COX-2 is induced by a wide variety of stimuli and was initially identified as an immediate-early growth response gene. In addition, COX-2 expression is markedly increased in 85-90% of human colorectal adenocarcinomas, whereas COX-1 levels remain unchanged. Several epidemiological studies have reported a 40-50% reduction in the risk of developing colorectal cancer in persons who chronically take such nonsteroidal antiinflammatory drugs (NSAIDs) as aspirin, which are classic inhibitors of cyclooxygenase. Genetic evidence also supports a role for COX-2, since mice null for COX-2 have an 86% reduction in tumor multiplicity in a background containing a mutated APC allele. These results strongly suggest that COX-2 contributes to the development of intestinal tumors and that inhibition of COX is chemopreventative.

Original languageEnglish (US)
Pages (from-to)72-83
Number of pages12
JournalAnnals of the New York Academy of Sciences
Volume889
DOIs
StatePublished - Jan 1 1999

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ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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