Abstract LB-85: Ectopic expression of eukaryotic translation elongation factor eEF1A2 is a hallmark for human lung cancer and is associated with poor prognosis

Abstract

Abstract Background: The elongation factor eEF1A is one of the most abundantly expressed cellular proteins. It exists in two forms, eEF1A2, expressed in neurons and striated muscle, and eEF1A1, expressed in all other cell types. No normal adult cell expresses both forms. We investigated their role in lung cancer. Methods: We studied over 500 NSCLC and SCLC lung cancers and over 170 cell lines, as well as corresponding non- malignant lung tissues and immortalized respiratory epithelial lines. Methods included microarray, qPCR, immunostaining and western blots for eEF1A1 and eEF1A2, genomic sequencing and SNP analyses. Results: All normal and malignant cells highly expressed eEF1A1. EEF1A2 was expressed in 70-80% of all forms of lung cancers and 95% of cell lines, while all non-malignant tissues were negative. Expression of eEF1A2 in neuroendocrine tumors was particular high. The ectopic expression of eEF1A2 was not the consequence of mutations or copy number gains. Use of demethylating agents and HDAC inhibitors resulted in expression of eEF1A2 in respiratory epithelial cells, indicating that epigenetic mechanisms prevented expression in non-malignant cells. Transient knockdown of the eEF1A2 expression inhibited proliferation and colony formation of lung cancer cell lines. Furthermore, the expression of eEF1A2 in resected NSCLC cancers was associated with poor survival. Conclusions: Highly specific ectopic expression of eEF1A2 gene is frequent in all types of lung cancer, plays an important role in tumor pathogenesis and is a potential diagnostic and prognostic factor. 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 LB-85. doi:1538-7445.AM2012-LB-85