Down-regulation of the erbB-2 receptor by trastuzumab decreases Akt kinase activation but not MAPK activation. Down-regulation of the erbB-2 receptor by trastuzumab decreases Akt kinase activation but not MAPK activation. A, two erbB-2-overexpressing cancer cell lines (SKBr-3 and MDA-MB-453) and two cell lines expressing low levels of erbB-2 receptor (MDA-MB-468 and MDA-MB-231) were incubated with trastuzumab (1 μm) for 4 days. Cell lysates were prepared and immunoblotted with antibodies to phospho-Akt (p-Akt), Akt, phospho-MAPK (p-MAPK), MAPK, and tubulin as indicated to the right. Tubulin is shown as a loading control. The bracket at the right indicates p-MAPK. The relative intensity of phosphorylation of erk1 and erk2 varied among different cell lines. Molecular weights (in thousands) are shown to the left. B, the erbB-2-overexpressing cell line SKBr-3 was transfected with antisense (AS) or sense (S) ODNs or mock-transfected (M). After transfection, cells were incubated for an additional 72 h. Lysates were prepared and immunoblotted with antibodies as described in A. Molecular weights (in thousands) are shown to the left. Mauricio Cuello et al. Cancer Res 2001;61:4892-4900 ©2001 by American Association for Cancer Research