Crosstalk between estrogen receptor alpha and the aryl hydrocarbon receptor in breast cancer cells involves unidirectional activation of proteasomes

2,3,7.8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental toxin that a ctivates the aryl hydrocarbon receptor (AhR) and disrupts multiple endocrin e signaling pathways. T47D human breast cancer cells express a functional e strogen receptor alpha (ER alpha) and AhR, and treatment of these cells wit h 17 beta-estradiol (E2) or TCDD resulted in a rapid proteasome-dependent d ecrease in immunoreactive ER alpha and AhR proteins (> 60-80%), respectivel y, E2 did not affect the AhR, whereas TCDD induced proteasome-dependent deg radation of both the. AhR and ER alpha in T47D and MCF-7 human breast cance r cells, and these responses were specifically blocked by proteasome inhibi tors. Thus, TCDD-induced degradation of ER alpha may contribute to the anti estrogenic activity of AhR agonists and this pathway may be involved in AhR -mediated disruption of other endocrine responses, (C) 2000 Federation of E uropean Biochemical Societies. Published by Elsevier Science B.V. All right s reserved.