fig3

Figure 3. The protein kinase RNA-like endoplasmic reticulum kinase (PERK)/nuclear factor κB (NF-κB)/tumor necrosis factor α (TNFα) axis is activated by E₂ to induce apoptosis in long term estrogen deprivation breast cancer cells. E₂ activates nuclear estrogen receptor α (ERα) and accumulates unfolded proteins in the endoplasmic reticulum, which activates PERK in response to the misfolded proteins. This stress kinase phosphorylates signal transducer and activator of transcription 3 (STAT3) and increases its DNA-binding activity. Subsequently, activated STAT3 promotes NF-κB DNA binding and induction of TNFα expression^[22]