Fig. 2.

EGFR signaling is responsible for SYK-mediated paclitaxel resistance. SYK activity affects lapatinib sensitivity. (A) EGFR^WT and mutant EGFR^3F (containing phenylalanine substitutions at Y869, Y1172, Y1197) were expressed in SKOV3 SYK^130E inducible Tet-off cells. Paclitaxel sensitivity was tested in 3-D spheroid culture. (B) Immunoblotting showing the expression of SYK^130E (GFP tag) and EGFR^WT or EGFR^3F (V5 tag) by cells tested in A. (C) SKOV3 SYK^130E Tet-off cells (±Tet) were treated with a range of lapatinib concentrations in 3-D spheroid cultures, and cell viability was examined one week later. (D) Growth curves of OVISE SYK^WT and syngeneic SYK^KO cells using the Sybr green cell proliferation assay. (E) mRNA expression of EGFR-regulated genes in OVISE SYK^WT and SYK^KO cells after stimulation with EGF (50 ng/mL) for 24 h. Cells were serum starved prior to EGF addition. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)