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RNA-seq of PC9 cells tolerant to gefitinib

ABSTRACT: RNA-seq of PC9 cells tolerant to gefitinib

PROVIDER: PRJNA482642 | ENA |

REPOSITORIES: ENA

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Transcriptome analysis of PC9 cells with gefitinib or/and hypoxia treatment and comparison with gefitinib resistant PC9 cells and ALDH positive PC9 cells

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RNA-seq of PC9 cells tolerant to gefitinib

Project description:EGFR inhibitors (EGFRi) are effective against EGFR mutant lung cancers. The efficacy of these drugs however is mitigated by the outgrowth of resistant cells, most often driven by a secondary acquired mutation in EGFR, T790M. We recently demonstrated that T790M can arise de novo during treatment (Hata et al., Nature Medicine 2016); it follows that one potential therapeutic strategy to thwart resistance would be identifying and eliminating these cells (referred to as drug tolerant cells (DTCs)) prior to acquiring secondary mutations like T790M. We have developed DTCs to EGFRi in EGFR mutant lung cancer cell lines. Subsequent analyses of DTCs included RNA-seq, high-content microscopy, and protein translational assays. Based on these results, we tested the ability of MCL-1 BH3 mimetics to combine with EGFR inhibitors to eliminate DTCs and shrink EGFR mutant lung cancer tumors in vivo.

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Analysis of gene expression change by gefitinib treatment in gefitinib sensitive PC9 and resistant PC9.

Project description:We established a gefitinib-resistant cell line (PC-9GR), by serial exposure of gefitinib to PC-9, an originally gefitinib-sensitive lung cancer cell line (PC-9na), for long period.We collected total RNA from both PC-9 and PC-9GR and examined mRNA expression profile, comprehensively. Gefitinib induced gene expression was measured in human lung cancer cell line was measured at 48 hours after exposure to 1uM Gefitinib.

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