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