Cyclooxygenase-2: a target for the prevention and treatment of breast cancer

L R Howe1,2, K Subbaramaiah2,3, A M C Brown1,2 and A J Dannenberg2,3

1Strang Cancer Research Laboratory, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
2Department of Cell Biology and Anatomy, Weill Medical College of Cornell University, New York, NY 10021, USA
3Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA
 
(Requests for offprints should be addressed to L R Howe; Email: lrhowe@med.cornell.edu)

Abstract

Cyclooxygenase-2 (COX-2), an inducible prostaglandin synthase, is normally expressed in parts of the kidney and brain. Aberrant COX-2 expression was first reported in colorectal carcinomas and adenomas, and has now been detected in various human cancers, including those of the breast. Strikingly, COX-2 overexpression in murine mammary gland is sufficient to cause tumor formation. To date, the role of COX-2 in tumorigenesis has been most intensively studied in the colon. Thus, the relationship between COX-2 and neoplasia can best be illustrated with reference to intestinal tumorigenesis. Here we consider the potential utility of selective COX-2 inhibitors for the prevention and treatment of breast cancer. Data for cancers of the colon and breast are compared where possible. In addition, the mechanisms by which COX-2 is upregulated in cancers and contributes to tumorigenesis are discussed. Importantly, several recent studies of mammary tumorigenesis in animal models have found selective COX-2 inhibitors to be effective in the prevention and treatment of breast cancer. Clinical trials will be needed to determine whether COX-2 inhibition represents a useful approach to preventing or treating human breast cancer.

Endocrine-Related Cancer


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Endocrine-Related Cancer


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