FIGURE 3. Differential sensitivity of glioma- versus lung cancer-specific EGFR mutants to the reversible EGFR inhibitors lapatinib and erlotinib.
A. Classification of reversible ATP-competitive EGFR kinase inhibitors based on crystal structures. B. Ectopic expression of glioma-specific EGFR EC mutants in EGFR-deficient (EGFR-NEG) NR6 fibroblasts. Shown are immunoblots of whole cell lystates. C. Enhanced sensitivity of EGFR EC mutants to lapatinib in NR6 cells. NR6 cells expressing the indicated alleles of EGFR were treated with increasing doses of erlotinib or lapatinib as shown. Cell lysates were made and analyzed by immunoblot with the indicated antibodies. D. Differential sensitivity of endogenously expressed glioma- versus lung cancer-specific EGFR mutants to lapatinib versus erlotinib. The indicated GBM (upper panels) and lung cancer (Lung Ca, lower panels) cell lines were treated with various doses of lapatinib or erlotinib. Cells were harvested and analyzed by western blot using antibodies for tyrosine-phosphorylated EGFR (pEGFR, top) or total EGFR (tEGFR, bottom). E and F. Differential cell death response of GBM (E) and lung cancer (F) cell lines to lapatinib versus erlotinib. Cell death was assessed by trypan blue exclusion assay after 5 days of incubation with the indicated drug.