COX-2 inhibitors for the prevention of breast cancer.

Abstract	The inducible prostaglandin synthase cyclooxygenase-2 (COX-2) is normally expressed predominantly in kidney and brain, and also has important roles in reproduction and inflammation. COX-2 misexpression has been observed in numerous human cancers, including the majority of colorectal cancers. Recently, COX-2 overexpression has been described in human breast cancer. COX-2 is present in about 40% of invasive breast carcinomas, particularly those that overexpress HER2/neu, and COX-2 expression correlates with poor patient prognosis. Manipulation of Cox-2 gene dosage by using transgenic overexpression and knockout approaches has revealed an important role for Cox-2 in tumorigenesis. Furthermore, translational experiments using rodent breast cancer models suggest COX-2 inhibition to be an effective strategy for both prevention and treatment of experimental breast cancers. Since COX-2 can contribute to multiple facets of tumorigenesis, including angiogenesis, several mechanisms are likely to underlie the anticancer action of COX inhibitors. Thus, selective COX-2 inhibitors offer considerable promise for the prevention and treatment of human breast cancer.
Authors	Louise R Howe, Andrew J Dannenberg
Journal	Journal of mammary gland biology and neoplasia (J Mammary Gland Biol Neoplasia) Vol. 8 Issue 1 Pg. 31-43 (Jan 2003) ISSN: 1083-3021 [Print] United States
PMID	14587862 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., Review)
Chemical References	Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors Isoenzymes Membrane Proteins Mutagens Prostaglandins Cyclooxygenase 2 PTGS2 protein, human Prostaglandin-Endoperoxide Synthases
Topics	Animals Apoptosis Breast Neoplasms (enzymology, prevention & control) Cell Line, Tumor Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors (pharmacology) Disease-Free Survival Female Humans Isoenzymes (metabolism) Membrane Proteins Mutagens Neovascularization, Pathologic Pregnancy Prognosis Prostaglandin-Endoperoxide Synthases (metabolism) Prostaglandins (metabolism) Rats Time Factors Transgenes Up-Regulation

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