Abstract 7: Knockdown of EGFR to investigate its therapeutic potential for treatment of non-small cell lung cancers

Abstract

Abstract Background: Epidermal growth factor receptor (EGFR) is a transmembrane protein consisting of an extracellular ligand-binding domain, and its activation leads to a multitude of effects including cell proliferation, cell differentiation, angiogenesis, metastasis, and antiapoptosis. EGFR can be a partner of heterodimer of other EGFR family such as HER2 and HER3. EGFR is often overexpressed in non-small cell lung cancer (NSCLC). Anti-EGFR agents including EGFR-tyrosine kinase inhibitors (EGFR-TKIs) have considered to be effective for NSCLC when drug sensitive EGFR mutation is present. However, inherent and acquired resistances are major problems of EGFR targeting therapies. In this study, we knock-downed EGFR using small interfering RNAs (siRNAs) in NSCLC cell lines to examine the significance of targeting EGFR for NSCLC therapy. Materials and methods: We treated 14 NSCLC cell lines including nine EGFR mutant and five EGFR wild-type cell lines by geftinib or siRNAs for EGFR knock-down (siR-EGFR). Three cell line, PC-9-GR-N1, RPC-9, and HCC827-Met, were experimentally established as acquired resistant cells to gefitinib. The anti-tumor effect was determined by MTS or colony formation assay. The protein expression was evaluated using Western blotting. Results: All cell lines showed the expression of EGFR protein and siR-EGFR treatment down-regulated EGFR protein in all 14 cell lines. siR-EGFR suppressed cell viability in 7 of 9 EGFR mutant cells ranged from 8.0% to 73%. PC-9-GR-N1 and RPC-9 also showed inhibition. NCI-H1670 and HCC827-Met harboured EGFR mutation but were not inhibited. Of note, PTEN was deleted in NCI-H1670 and c-MET was amplified in HCC827-Met. Cell viability of all EGFR wild-type cells was not inhibited except NCI-H411. Conclusion: Our results indicated that EGFR can be the therapeutic target of NSCLC with EGFR activation. By contrast, targeting EGFR is not appropriate strategy for tumor of which EGFR is not activated even though EGFR is expressed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 7. doi:1538-7445.AM2012-7