Journal
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
Volume 102, Issue 1-5, Pages 241-249Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jsbmb.2006.09.029
Keywords
breast cancer; inflammation; cyclooxygenase 2; aromatase; nuclear factor kappa B; progesterone receptor
Funding
- NICHD NIH HHS [P01 HD011149, 5 P01 HD011149] Funding Source: Medline
- NIDDK NIH HHS [R01 DK031206, 2 R01 DK031206] Funding Source: Medline
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There is convincing evidence to suggest that estrogen and inflammatory mediators play important roles in growth and progression of breast cancer. Moreover, local conversion of androgens to estrogens by aromatase (product of CYP19 gene) occurs in 70% of all breast cancers. The actions of aromatase in both the breast tumor and in surrounding adipose stromal and endothelial cells can result in high local levels of estrogen production that stimulate tumor growth. The efficacy of current endocrine therapies is predicted only if the tumor contains significant amounts of ER. Presence of PR in the tumor also is an important predictor of tumor aggressiveness and responsiveness to endocrine therapy. Immunoreactivity for aromatase in human breast tumors is highly correlated with that for cyclooxygenase 2 (COX-2), the rate-determining enzyme in prostanoid biosynthesis. COX-2 expression also is correlated with expression of HER-2/neu, an oncogene expressed in > 30% of breast tumors. In this manuscript, we will review findings to suggest that induction of COX-2 by inflammatory cytokines acting through NF-kappa B contributes to the increase in CYP19 expression and breast cancer progression, and that PR plays a dominant protective role in breast cancer cells by antagonizing NF-kappa B activation of COX-2. (c) 2006 Elsevier Ltd. All rights reserved.
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