Fig. 5

Modulation of oxidative status and leptin signalling pathway in human mammary epithelial cells. Leptin, via its receptor Ob-R, activated several signalling pathways such as PI3K/AKT parallel to JAK/STAT cascade. This resulting in modulation of cell growth, cell survival, oxidative status and inflammation. Depending of the neoplastic status of cells, oxidative status could also modulate these pathways through glutathionylation and protein disulphides. a: in healthy cells, due to the high antioxidant status, growth and survival pathways could be attenuated by glutathionylation and protein disulphides. Thus, leptin signalling favours preferentially the induction of antioxidant defences and of inflammation. b: in neoplastic ER+ cells, the intermediate antioxidant status was not sufficient to attenuate cell growth and survival pathways. Thus, in the presence of leptin all the signalling pathways could be induced, resulting in a stimulation of growth, survival, antioxidant defences and inflammation. c: in triple-negative cells, the high ROS production associated to the lower antioxidant status could favour growth, survival, and inflammation pathways in presence of leptin. Results of this study are draw in black. Data from previous report are shown in grey. Stimulation effect is flagged by + and inhibitor effect is flagged by -. JAK: Janus kinase; Ob-R: leptin receptor; PI3K: phosphor-inositol-3-kinase; STAT3: signal transducer and activator of transcription 3; GR: glutathione reductase; GST: glutathione S transferase; GPx: glutathione peroxidase; HO-1: heme oxygenase 1; COX-2: cyclo-oxygenase 2