(A) HCC827 cells infected with a lentivirus expressing a Tet-inducible shERBB3 hairpin were induced with 100ng/mL doxycycline (+Dox) for 48hrs. Following knockdown, cells were treated with AZD6244 (2µM) for the indicated number of hours. Cell lysates were immunoblotted to detect the indicated proteins. (B) BT-474 cells were transfected with control or ERBB3 targeted siRNA for 48hrs, followed by treatment with AZD6244 for 6hrs. Cell lysates were immunoblotted with the indicated proteins. (C) BT-474 cells were transfected with control or ERBB3 targeted siRNA for 48hrs, followed by treatment with 2µM AZD6244, 1µM of the PI3K inhibitor GDC-0941, or the combination for 72hrs. Cells were collected and stained for propidium iodide and AnnexinV to determine the percentage of apoptotic cells. Each data point represents the mean ±SD of three independent experiments.