Induction of apoptosis following depletion of SREBP in cancer cells is restricted to lipoprotein deplete conditions. (A) RPE-myrAkt-ER cells were transfected with 25 nM siRNA oligonucleotides targeting SREBP1, SREBP2 or a combination of both. After 48 hours, cells were placed in medium containing 10% FCS or 1% LPDS for a further 48 hours in the presence of 100 nM 4-OHT or solvent (ethanol). Cell viability was determined by measuring caspase 3/7 activity (Apoptosis) normalized to total protein content (SRB). Graph shows mean ± SEM of three independent experiments. (B) The effect of SREBP depletion on cell viability in breast cancer cells. Cells were treated and analyzed as in A. Graphs show mean ± SEM of three independent experiments. Cell lines carry different mutations in components of the PI3-kinase pathway: MCF7 (PIK3CA E545K), T47D (PIK3CA L194F), HCC1954 (PIK3CA H1047R), BT549 (PTENnull), MDA-MB-468 (PTENnull), MDA-MB-231 (KRAS G13D) and SKBR3 (HER2 amplification). Information on cancer gene mutations was obtained from the Wellcome Trust Sanger Institute Cancer Genome Project (http://www.sanger.ac.uk/genetics/CGP). (C) Effect of depletion of SREBP1 or SREBP2 on viability of U87 glioblastoma cells. Graph shows mean ± SEM of three independent experiments. *P < 0.05; **P < 0.01.