Aryl hydrocarbon receptor: An emerging player in breast cancer pathogenesis and its potential as a drug target (Review)

Abstract

Breast cancer is the most common malignancy in women. Metastatic breast cancer is incurable and is a major cause of shortened patient survival. The different molecular types of breast cancer make targeted therapy difficult and a complex challenge. aryl hydrocarbon receptor (ahr) is an evolutionarily conserved transcription factor that has been implicated in the metabolism of xenobiotic ligands. ahr is activated by numerous exogenous and endogenous ligands and participates in multiple physiological processes, including proliferation, migration, invasion and apoptosis. ahr expression is upregulated in certain breast cancer subtypes, including estrogen receptor-positive breast cancer, and has been implicated in the development and progression of breast cancer. over the last two decades, ahr and its ligands have emerged as novel biological targets for the treatment of breast cancer. Both ahr agonists and antagonists may be effective in inhibiting critical activities of breast cancer. The present review evaluates the role and underlying mechanisms of ahr and its ligands in breast cancer and demonstrates the potential of exploiting ahr as a novel target for breast cancer therapy. Contents1. introduction 2. association between ahr and breast cancer 3. ahr pathways in breast cancer 4. ahr ligands exhibit tumor-suppressive properties 5. ahr and its ligands promote mammary carcinogenesis 6. discussion 7. conclusion

The Garlic Compound, Diallyl Trisulfide, Attenuates Benzo[a]Pyrene-Induced Precancerous Effect through Its Antioxidant Effect, AhR Inhibition, and Increased DNA Repair in Human Breast Epithelial Cells

“…AhR forms a heterodimer complex (AhR/ARNT) by binding to the xenobiotic responsive elements (XRE), where transcription is initiated in conjunction with the hypoxia-responsive elements (HRE) [ 40 ]. B[a]P is a main ligand of AhR that directly binds to the receptor and induces its biological effects associated with carcinogenesis in cancer and the development and progression of breast cancer [ 41 , 42 ]. In this study, AhR expression was significantly ( p < 0.0001) induced following 24 h exposure to 1 μM B[a]P. The CoTx significantly decreased ( p < 0.0001) the AhR response at the same time point, thus attenuating the AhR expression in B[a]P-treated breast epithelial cells.…”