Mechanisms and therapeutic advances in the management of endocrine-resistant breast cancer

Figure 1 Estrogen receptor action at molecular level. A: Ligand dependent activation: in classic estrogen signaling, ligand-bound ER activates gene expression-either through direct binding of dimeric ER to specific DNA response elements in complexes including co-activators, or function as a coregulator through protein - protein interactions with other transcription factors to facilitate binding to serum response elements and activation of transcription; B: Ligand independent activation: the ER can also be activated by ligand independent fashion, as a consequence of signaling events downstream of membrane receptor tyrosine kinases (RTKs); C: Non-genomic mechanisms: signaling can be mediated through non-genomic mechanisms by ER that is localized at the cell membrane or in the cytoplasm. ER: Estrogen receptor; mTOR: Mammalian target of rapamycin; FGFR: Fibroblast growth factor receptor; IGF-1R: Insulin-like growth factor-1 receptor; EGFR: Epidermal growth factor receptor.