Compensatory Estrogen Signal Is Capable of DNA Repair in Antiestrogen-Responsive Cancer Cells via Activating Mutations

Figure 2

Emergency response to tamoxifen (T) treatment in tumor cells. The rapid translocation of unbound estrogen receptors (ERs) out of the nucleus facilitates their interactions with membrane-associated growth factor receptors (IGF1-R and EGFR) inducing their unliganded activation. Activated cytoplasmic ERs initiate rapid transcriptional processes in the nucleus through transcriptional factors (TFs). Growth factor- (GF-) activated GFRs may also induce unliganded activation on nuclear unbound ERs driving their transcriptional activity. E: estrogen; P: phosphorylation; N: nucleus; red arrow: activation; black arrow: inhibition.