Abstract
Abstract Gain of chromosome 3q26-28 is one of the most common genomic imbalances in non-small cell lung cancer (NSCLC), particularly in squamous cell carcinomas (SCC). A comprehensive approach combining array CGH, mircroarray expression and shotgun proteomics data analysis reveals amplification, overexrpession of a candidate gene on 3q26, fragile-X-mental-retardation-related protein 1 (FXR1) in lung cancer. FXR1 is amplified and overexpressed in NSCLC tumors and highly correlated with several 3q26-28 targets including epithelial cell transforming sequence 2 (ECT2), protein kinase C iota (PKCi) and eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) measured by Real time-PCR and immunohistochemistry. We hypothesized that FXR1 is associated with these oncogenes and plays a critical role in lung cancer progression. ECT2 is known to promote lung cancer by binding to PKCi and activating MAPK signaling pathway. We found that overexpressing FXR1 in an immortalized human bronchial epithelial cell line (HBEC3KT) leads to upregulated expression of ECT2, PKCi and ERK1/2 activity. Downregulation of FXR1 using siRNA in lung cancer cell lines H520 and HCC95 induces the decreased expression of ECT2, PKCi and EIF4G1. Immunoprecipitation confirms that FXR1 binds to PKCi and EIF4G1 in NSCLC cells. Loss of FXR1 using siRNA treatment inhibits cell growth and survival of NSCLC cells that harbor 3q26-28 amplicon. Our results demonstrate the oncogenic potential of FXR1 and supports the concept that amplified targets on 3q26-28 are genetically and functionally associated to drive lung cancer cell growth. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3043. doi:10.1158/1538-7445.AM2011-3043
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