The role of COX-2 in intestinal cancer.

Williams C, Shattuck-Brandt RL, DuBois RN
Ann N Y Acad Sci. 1999 889: 72-83

PMID: 10668484 · DOI:10.1111/j.1749-6632.1999.tb08725.x

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.

MeSH Terms (15)

Animals Anti-Inflammatory Agents, Non-Steroidal Aspirin Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors Gene Expression Regulation, Neoplastic Genetic Predisposition to Disease Humans Intestinal Neoplasms Isoenzymes Membrane Proteins Mice Mice, Knockout Prostaglandin-Endoperoxide Synthases

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