Activation of IGFBP7 Drives Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibition in Lung Cancer

Previous study has demonstrated that HCC827/gef cells are resistant to gefitinib-induced aspoptosis. To investigate the regulators contributed to gefitinib resistance in lung cancer, we analyzed the gene expression profiles between HCC827 andHCC827/gef cells. Reduced IGFBP7 in TKI-resistant cells reversed resistance to EGFR-TKIs, and increased EGFR-TKI-induced apoptosis through up-regulation of BIM and activation of caspases. Suppression of IGFBP7 attenuated phosphorylation of IGF-IR and downstream AKT in TKI-resistant cells. RNAs extracted from gefitinib-sensitive HCC827 cells and gefitinib-resistant HCC827/gef cells were hybridized on Affymetrix microarrays. We tried to compare the differential gene expression profiles between HCC827 and HCC827/gef cells to identify the possible regulators in gefitinib resistance.