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

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 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.

• Authors: L R Howe, K Subbaramaiah, A M Brown, A J Dannenberg
• Journal: Endocrine-related cancer (Endocr Relat Cancer) Vol. 8 Issue 2 Pg. 97-114 (Jun 2001) ISSN: 1351-0088 [Print] England
• PMID: 11397667 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors
• Isoenzymes
• Membrane Proteins
• Pyrazoles
• Sulfonamides
• Cyclooxygenase 2
• PTGS2 protein, human
• Prostaglandin-Endoperoxide Synthases
• Celecoxib

Topics

• Animals
• Breast Neoplasms (drug therapy, enzymology, prevention & control)
• Celecoxib
• Colorectal Neoplasms (drug therapy, enzymology, prevention & control)
• Cyclooxygenase 2
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors (therapeutic use)
• Female
• Gene Expression Regulation, Enzymologic
• Gene Expression Regulation, Neoplastic
• Humans
• Isoenzymes (antagonists & inhibitors, biosynthesis, physiology)
• Membrane Proteins
• Prostaglandin-Endoperoxide Synthases (biosynthesis, physiology)
• Pyrazoles
• Sulfonamides (therapeutic use)
• Up-Regulation