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

Abstract

Cyclooxygenase-2 (COX-2) is an important pharmacological target with great promise in the prevention and treatment of colorectal cancer (CRC). The mechanism underlying COX-2 overexpression in CRC is unresolved. On the basis of 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 transcription. We identified 13 c-Myb binding sites in the human COX-2 promoter. Eight of these sites were moderate to high-affinity DNA binding targets. Promoter studies indicated that c-Myb can activate COX-2 transcription, whereas dominant-negative Myb mediated repression. These data provide the first rational basis for overexpression of COX-2 in CRC and offer an additional potential target for managing this disease.