Abstract 1840: Contribution of miR-205 in gefitinib-resistant lung cancer cell lines

Abstract

Abstract Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), gefitinib is effective therapies for patients with advanced non-small cell lung cancer (NSCLC). Treatment with gefitinib frequently induces drug resistance in NSCLC. Two mechanisms of acquired resistance have been validated in patients. Secondly mutations in EGFR itself, EGFR T790M and amplification of the MET oncogene are observed in resistance case. However, it remains unclear how MET over expression contributes to TKI resistant NSCLC. Recently, micro RNA (miRNA) expression is noted and analyzed because the concern of these molecules in cancer pathogenesis and drug resistance has been elucidated. Circulating tumor cell (CTC) and miRNA are focused as sensitive and non-invasive biomarkers for cancer diagnosis. In this study, we aimed at the miRNA in the gefitinib-resistant cell lines, and evaluated the miRNAs being associated with resistance of gefitinib. We established gefitinib resistant cell lines, in which MET is amplified, PC-9/MET and PC-9/MET-1K by a stepwise escalation of gefitinib concentrations in vitro. Microarray and real time PCR analysis indicated that miR-205 is significantly elevated in both resistant cell lines, and ErbB3 was a significant target. We examine further to reveal that relation between miR-205 and EGFR family, such as ErbB2 and ErbB3. Our results suggest that miR-205 may function as a gefitinib resistance in NSCLC. Citation Format: Toshihiro Suzuki, Ikuko Nagasawa, Toshimitsu Yamaoka, Tohru Ohmori, Kazuto Nishio, Kiyotaka Koyama, Yuki Ogasawara. Contribution of miR-205 in gefitinib-resistant lung cancer cell lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1840. doi:10.1158/1538-7445.AM2014-1840