Abstract
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-κB 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-κB activation of COX-2.
Original language | English (US) |
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Pages (from-to) | 241-249 |
Number of pages | 9 |
Journal | Journal of Steroid Biochemistry and Molecular Biology |
Volume | 102 |
Issue number | 1-5 SPEC. ISS. |
DOIs | |
State | Published - Dec 2006 |
Keywords
- Aromatase
- Breast cancer
- Cyclooxygenase 2
- Inflammation
- Nuclear factor κB
- Progesterone receptor
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Endocrinology
- Clinical Biochemistry
- Cell Biology