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

FEBS Letters

Safe, Stephen¹  Saville, Brad¹  Stoner, Matthew¹  Wormke, Mark¹ 

[1] Department of Veterinary Physiology and Pharmacology, and Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843-4466, USA

关键词: Proteasome;    Estrogen receptor α;    Aryl hydrocarbon receptor;    Degradation;    Crosstalk;    Breast cancer cell;   

DOI  :  10.1016/S0014-5793(00)01830-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental toxin that activates the aryl hydrocarbon receptor (AhR) and disrupts multiple endocrine signaling pathways. T47D human breast cancer cells express a functional estrogen receptor α (ERα) and AhR, and treatment of these cells with 17β-estradiol (E2) or TCDD resulted in a rapid proteasome-dependent decrease in immunoreactive ERα and AhR proteins (>60–80%), respectively. E2 did not affect the AhR, whereas TCDD induced proteasome-dependent degradation of both the AhR and ERα in T47D and MCF-7 human breast cancer cells, and these responses were specifically blocked by proteasome inhibitors. Thus, TCDD-induced degradation of ERα may contribute to the antiestrogenic activity of AhR agonists and this pathway may be involved in AhR-mediated disruption of other endocrine responses.

【 授权许可】

Unknown