Genomic aberrations associated with erlotinib resistance in non-small cell lung cancer cells.

BACKGROUND/AIM: Mechanisms of resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) are not fully-understood. In this study we aimed to elucidate remaining unknown mechanisms using erlotinib-resistant NSCLC cells.

MATERIALS AND METHODS

We performed array comparative genomic hybridization (aCGH) to identify genomic aberrations associated with EGFR-TKI resistance in erlotinib-resistant PC-9ER cells. Real-time polymerase chain reaction (PCR) and immunoblot analyses were performed to confirm the results of aCGH.

RESULTS

Among the five regions with copy number gain detected in PC-9ER cells, we focused on 22q11.2-q12.1 including v-crk avian sarcoma virus CT10 oncogene homolog-like (CRKL), the overexpression of which seemed to be associated with EGFR-TKI resistance. Blockade of downstream phosphatidylinositol 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homolog (AKT) signaling using NVP-BEZ235 suppressed the proliferation of PC-9ER cells, implying the involvement of acquired CRKL amplification in EGFR-TKI resistance.

CONCLUSION

Acquired CRKL amplification was identified as contributing to EGFR-TKI resistance; this cell line model can be utilized to study this resistance mechanism.