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

Figure 3

Mechanism of tumor response in cancer cells treated with tamoxifen (T). Abundant unliganded estrogen receptor (ER) activation increases the expression of estrogen-regulated genes upregulating the circuit of ER-aromatase-E2-ER expression. In the meantime, growth factors (GFs) activate growth factor receptors (GFRs) activating free nuclear ERs via an unliganded pathway. The predominance of estrogen- (E-) bound ERs over T-bound ones leads to DNA repair, apoptotic death, and clinical tumor response. P: phosphorylation; N: nucleus; red arrow: activation; black arrow inhibition.