Research Paper Volume 10, Issue 12 pp 4000—4023

The ER-alpha mutation Y537S confers Tamoxifen-resistance via enhanced mitochondrial metabolism, glycolysis and Rho-GDI/PTEN signaling: Implicating TIGAR in somatic resistance to endocrine therapy

Figure 8. Mitochondrial biogenesis and membrane potential are increased in MCF7-Y537S cells, in the presence of 4-OHT. To determine the possible effects of the Y537S mutation on mitochondrial biogenesis and membrane potential, MCF7-Y537S cells were subjected to flow-cytometry, using MitoTracker probes. FACS analysis was carried out on MCF7 transfected cells after pre-treatment with 4-OHT. (Panels A and B) Note that MCF7-Y537S and MCF7-Y537SN cells show a significant increase in mitochondrial mass (MitoTracker Deep-Red), but an increased mitochondrial membrane potential (MitoTracker Orange) was observed only in MCF7-Y537S cells in growth media with 4-OHT (1 µM). (Panel C) Finally, the ratio (activity/mass) of mitochondrial membrane potential (MitoTracker Orange) and mitochondrial mass (MitoTracker Deep-Red) was increased only in MCF7-Y537S cells, in growth media containing 4-OHT. ** p < 0.001; *** p 0.0001; ns = not significant.