Cyclooxygenase-2, a colorectal cancer nonsteroidal anti-inflammatory drug target, is regulated by c-MYB

Cyclooxygenase-a (COX-2) Is an important pharmacological target with great promise in the prevention and treatment of colorectal cancer (CRC), The mec hanism underlying COX-2 overexpression in CRC is unresolved. On the basis o f the coincident high levels of the transcription factor c-MYB and COX-2 in CRC, we hypothesized that c-MYB is a candidate activator of COX-2 transcri ption. We identified 13 c-Myb binding sites in the human COX-2 promoter, Ei ght of these sites were moderate to high-affinity DNA binding targets. Prom oter studies indicated that c-Myb fan activate COX-2 transcription, whereas dominant-negative Myb mediated repression. These data provide the first ra tional basis for overexpression of COX-2 in CRC and offer an additional pot ential target for managing this disease.