Revising the role of the androgen receptor in breast cancer
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Figure 1
Potential mechanisms of crosstalk between the androgen receptor and oestrogen receptor α pathways. (1) In classical ERα signalling, the ligand-bound receptor binds to specific DNA sequences (oestrogen response elements (EREs)) found in the regulatory regions of target genes, and via the recruitment of a complex of accessory proteins (coactivators) and the general transcription machinery, initiates gene transcription. (2) ERα also regulates gene transcription through interaction with transcription factors that tether the receptor to DNA. (3) The AR and ERα have been found to directly interact and this interaction is inhibitory to the transcriptional activity of both receptors. (4) The AR can bind to EREs and hence there may be competition for DNA occupancy. (5) ERα and AR share common coactivator proteins and hence through sequestration of accessory proteins, the AR may reduce ERα signalling. (6) ERα also has non-genomic actions, with membrane-bound receptors able to regulate protein kinase cascades (e.g. MAPK). (7) The AR has a similar non-genomic activity and competition for accessory proteins (e.g. MNAR), important in this signalling, may inhibit receptor activity.
- © 2014 Society for Endocrinology
