Figure 6

Cholesterol-rich lipid microdomains are involved in α-TEA + TAM circumvention of TAMR. (a) MCF-7/TAMR and MCF-7/HER-2 cells were treated with α-TEA at 20 μM for 15 hours. Identification of cholesterol-rich microdomains was determined by staining the cells with fluorescein-tagged cholesterol marker Filipin and images viewed by using a fluorescence microscope. (b) MCF-7/TAMR cells were pretreated with 10 μM exogenous cholesterol for 2 hours, followed by treatment with 20 μM α-TEA or 20 μM α-TEA plus 1 μM TAM for l day. Western blot analyses were performed to determine treatment effects on prosurvival signaling mediators and PARP cleavage. (a, b) Data are representative of three independent experiments. α-TEA, RRR-α-tocopherol ether-linked acetic acid analogue; MCF-7/HER-2, clone 18 MCF-7 cells overexpressing HER-2; MCF-7/TAMR, acquired tamoxifen-resistant MCF-7; PARP, poly (ADP-ribose) polymerase; TAM, tamoxifen; TAMR, tamoxifen resistant.