Journal
JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA
Volume 8, Issue 1, Pages 31-43Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1023/A:1025731204719
Keywords
COX-2; HER2/neu; chemoprevention; prognostic indicator; prostaglandin; angiogenesis; breast cancer
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Funding
- NATIONAL CANCER INSTITUTE [R01CA089578] Funding Source: NIH RePORTER
- NCI NIH HHS [CA089578] Funding Source: Medline
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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.
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