The role of COX-2 in intestinal cancer

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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 whereas 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 while 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 non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, which are classic inhibitors of COX. Genetic evidence also supports a role for COX-2, since mice null for COX-2 have an 86% reduction in tumour multiplicity in a background containing a mutated APC allele. These results strongly suggest that COX-2 contributes to the development of intestinal tumours and that inhibition of COX is chemopreventative. It is hoped that the chemopreven...