Mechanism of Resistance and Novel Targets Mediating Resistance to EGFR and c-Met Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer
Fig 5
Downregulation of Wnt proteins and upregulation of mTOR proteins in H1975 EGFR-mutant cells compared H2170-ER and H2170-SR cells.
H1975, H2170-ER and H2170-SR cells were plated at 125,000 cells per dish in 35 mm dishes and starved (RPMI 1640 with 0.5% BSA) for 24 hours before ligand (EGF and HGF) or/and drug (erlotinib and SU11274) treatments and were analyzed using western blot. (A) GATA-6 and p-LRP5/6 were observed to be downregulated in H1975 cells when compared to H2170 ER cells in same treatments. However, p-ERK, p-mTOR and p-p70S6K were upregulated in H1975 cells when compared to H2170-ER cells in similar treatments (n≥3, p<0.05). (B) Active β-catenin and GATA-6 were observed to be downregulated in H1975 cells compared to same treatments in H2170-SR cells. We also observed that p-ERK, p-mTOR and p-p70S6K were upregulated in H1975 cells when compared to H2170-SR cells in same treatments. The fold changes were calculated using ImageJ software (n≥3, p<0.05).