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.

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@article{Serizawa2013GenomicAA, title={Genomic aberrations associated with erlotinib resistance in non-small cell lung cancer cells.}, author={Masakuni Serizawa and Toshiaki Takahashi and Nobuyuki Yamamoto and Yasuhiro Koh}, journal={Anticancer research}, year={2013}, volume={33 12}, pages={5223-33} }