Redox signalling to nuclear regulatory proteins by reactive oxygen species contributes to oestrogen-induced growth of breast cancer cells

摘要: Historically, a majority of breast cancer research has focused on exploring conventional oestrogen receptor (ER) and growth factor pathways with limited investigations alternative mechanisms action. Redox signalling as an mechanism oestrogen-dependent tumor is rapidly emerging the promise therapeutic potential. Physiologically achievable concentrations increase reactive oxygen species (ROS) formation in cells (Felty et al, 2005a; Parkash 2006). An increasing body evidence supports postulate that oxidative stress generated from exposure to oestrogen, either directly or by influencing ER, may be important driver development evolution human (Okoh 2011; Penny Roy, 2013). The role ROS not new; however, gap knowledge currently exists regard how oestrogen-induced signals nuclear regulatory proteins way redox-sensitive proteins. It widely believed impaired redox pathway leads dysregulated phosphorylation and/or dephosphorylation involved activation deactivation We have previously shown 17β-estradiol (E2)-induced DNA synthesis MCF-7 depends mitochondrial oxidant AP-1, CREB, NRF-1 This study aims extend our previous efforts understanding E2 transduces signal well identify key downstream responsible for cells. demonstrate first time molecular E2-induced leading upregulation cell cycle genes; addition, impairment p27 activity through ROS-inducible PI3K→PDK1/2→AKT signal-transduction necessary E2-mediated