Inhibitory aryl hydrocarbon receptor-estrogen receptor alpha cross-talk and mechanisms of action.
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Inhibitory AhR-ER cross-talk has been observed in the rodent uterus, rodent mammary tumors, breast, ovarian, and endometrial cancer cell lines. There is evidence to support several mechanisms for interactions between these two signaling pathways, and these may be gene/response- and cell context-dependent. Recent data obtained in ER-positive breast cancer cells suggest that in cells cotreated with E2 plus TCDD, there is rapid proteasome-dependent degradation of ER, which then becomes limiting. Similar effects have been observed in the mouse uterus (144). These data do not exclude other mechanisms, which may differentially contribute to inhibitory AhR-ER cross-talk. These studies provide an example of the complexities of cross-talk between different biochemical/endocrine pathways and also demonstrate that the AhR is a target for development of drugs for treatment of breast and endometrial cancer.