Grant: Operating Grant

Breast cancer is the most common non-skin cancer and second leading cause of cancer death in Canadian women. Although breast cancer is significantly influenced by genetics, the risk of breast cancer is influenced by lifestyle and environment. Exposure to certain chemicals is suspected to contribute to increases in the risk of developing breast cancer. The aryl hydrocarbon receptor (AHR) and estrogen receptor alpha (ERalpha) are two proteins that play key physiological roles in cells, but are also implicated in diseases such as breast cancer. AHR mediates most, if not all, of the toxic effects of environmental contaminants called dioxins, whereas ERalpha is the key regulator of estrogen action and an important pharmaceutical target for breast cancer therapy. Previous studies have shown that these two proteins and their associated networks interact with each other and that this interplay is regulated by activation of AHR by dioxins. However, the molecular mechanisms remain elusive. The overall objective of this study is to elucidate the mechanisms of reciprocal interplay between AHR and ERalpha. To attain this objective, we will use molecular and cellular biology techniques in conjunction with biochemical approaches and animal models to better understand of the AHR/ERalpha interplay. These results will enable better estimates of the health risks associated with the combined environmental and dietary exposure to modulators of AHR and ERalpha activity and clarify the role of AHR in diseases such as breast cancer.