Cyclooxygenase-2: a target for the prevention and treatment of breast cancer.
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 tumour 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.
Howe
L R
LR
Strang Cancer Research Laboratory, Rockefeller University, Box 231, 1230 York Avenue, New York, New York 10021, USA. lrhowe@med.cornell.edu
Subbaramaiah
K
K
Brown
A M
AM
Dannenberg
A J
AJ
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000517:prevention & control; D000068579:Celecoxib; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000517:prevention & control; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000502:physiology; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000502:physiology; D011720:Pyrazoles; D013449:Sulfonamides / Q000627:therapeutic use; D015854:Up-Regulation
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib