jshs

Journal of Steroids & Hormonal Science

ISSN - 2157-7536

Abstract

The Aryl-hydrocarbon Receptor (AhR) as a Therapeutic Target in Human Breast Cancer

Julie M Hall

Breast cancer is currently the most prevalent malignancy among women in industrialized countries, and 1 in 8 women living in the United States will develop the disease at some point in her lifetime. Although the incidence of breast cancer has increased 0.3% per year since 1990, the mortality rate has decreased by 2% per year since 1990 due to improvements in treatment and early detection. New treatment strategies and a better molecular understanding of the disease will be important to continue the progress science has made against this disease. The aryl-hydrocarbon receptor (AhR) has been traditionally associated with activation by environmental contaminants, acute toxicity, and cancer risks associated with exposures. However, the AhR has been highly conserved throughout evolution suggesting an important biological role for the receptor independent of its response to environmental contaminants. There is a significant body of evidence indicating the AhR plays a role in breast epithelial cell differentiation and that receptor agonists can inhibit breast cancer growth. A 50% reduction in estrous-induced terminal end buds was observed in the mammary glands of AhR knockout animals when compared to wild type suggesting a role for the AhR in mammary development. In 2 independent rodent cancer bioassays, treatment with the AhR agonist 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) significantly reduced the incidence of spontaneous rat mammary tumors. These and other studies support the premise that the AhR plays a fundamental role in breast epithelial cell differentiation. This review provides a brief summary of the current evidence that the AhR may be an important pharmacological target for treating human breast cancer.

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