Cyclooxygenase-2, a colorectal cancer nonsteroidal anti-inflammatory drug target, is regulated by c-MYB.
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.
Ramsay
R G
RG
Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia. r.ramsay@pmci.unimelb.edu.au
Friend
A
A
Vizantios
Y
Y
Freeman
R
R
Sicurella
C
C
Hammett
F
F
Armes
J
J
Venter
D
D
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics; D051546:Cyclooxygenase 2; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism*; D051381:Rats; D014158:Transcription, Genetic
D007527:Isoenzymes; D008565:Membrane Proteins; D020598:Proto-Oncogene Proteins c-myb; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015500:Chloramphenicol O-Acetyltransferase