Figure 6.
Effects of PI3K inhibitors on lipid kinase activity and pAkt abundance. (A) Lipid kinase activity associated with MT immunoprecipitates in MT tumor-derived MMECs treated with various PI3K inhibitors (GDC-0941, 0.1 μM; A66, 0.1 μM; and TGX-221, 0.25 μM) as indicated following growth factor starvation. The bars represent relative lipid kinase activity ± SD (n = 6). (*) P < 0.05; (**) P < 0.001 (Student's t-test). (B) Lipid kinase activity associated with HER3 immunoprecipitates in NeuT tumor-derived MMECs treated with various PI3K inhibitors (GDC-0941, 0.1 μM; A66, 0.1 μM; and TGX-221, 0.25 μM) as indicated. The bar graph represents relative lipid kinase activity ± SD (n = 6). (*) P < 0.05; (**) P < 0.001 (Student's t-test). (C) Western blot analyses of pAkt in MMTV-MT tumor-derived cells treated with various PI3K inhibitors (in micromolar) as indicated following growth factor starvation. The bar graphs show the relative amounts of pAkt(T308) ± SD (n = 6). (*) P < 0.01; (**) P < 0.001 (Student's t-test). (D) Western blot analyses of pAkt in MMTV-NeuT tumor-derived cells treated with various PI3K inhibitors (in micromolar) as indicated. The bar graphs show the relative amounts of pAkt(T308) ± SD (n = 6). (*) P < 0.01; (**) P < 0.001 (Student's t-test). (E) Schematic diagram illustrating that p110β remains associated with the receptor complex in the presence of a p110β inhibitor, thus blocking the increased p110α binding and increased signal output observed in the p110β knockout scenario.