The role of COX-2 in intestinal cancer.
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 anti-inflammatory 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 chemo-preventative.
Williams
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Department of Cell Biology, Vanderbilt School of Medicine, Nashville, Tennessee 37232, USA.
Shattuck-Brandt
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DuBois
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D007414:Intestinal Neoplasms / Q000201:enzymology* / Q000209:etiology / Q000235:genetics / Q000517:prevention & control; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin