Document Detail


Cyclooxygenase-2, a colorectal cancer nonsteroidal anti-inflammatory drug target, is regulated by c-MYB.
MedLine Citation:
PMID:  10766162     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
R G Ramsay; A Friend; Y Vizantios; R Freeman; C Sicurella; F Hammett; J Armes; D Venter
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer research     Volume:  60     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2000 Apr 
Date Detail:
Created Date:  2000-05-04     Completed Date:  2000-05-04     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1805-9     Citation Subset:  IM    
Affiliation:
Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia. r.ramsay@pmci.unimelb.edu.au
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Binding Sites
Cell Line
Chloramphenicol O-Acetyltransferase / genetics
Colorectal Neoplasms / enzymology,  genetics
Cyclooxygenase 2
Gene Expression Regulation, Enzymologic*
Gene Expression Regulation, Neoplastic*
Humans
Isoenzymes / genetics*
Membrane Proteins
Molecular Sequence Data
Promoter Regions, Genetic*
Prostaglandin-Endoperoxide Synthases / genetics*
Proto-Oncogene Proteins c-myb / metabolism*
Rats
Transcription, Genetic*
Chemical
Reg. No./Substance:
0/Isoenzymes; 0/Membrane Proteins; 0/Proto-Oncogene Proteins c-myb; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/PTGS2 protein, human; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases; EC 2.3.1.28/Chloramphenicol O-Acetyltransferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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