Abstract 1749: Role of Eif3a in DNA Repair and Lung Cancer Chemo Sensitivity

Abstract Drug resistance is one of the major obstacles in successful chemotherapy of lung cancers. However, the mechanism of resistance is not yet clearly understood. Recently, eIF3a that plays an important role in translational control and regulation of gene expression was found to correlate negatively with prognosis in human cervical and esophageal cancers. We, thus, hypothesize that eIF3a may be an important factor in lung cancer response to chemotherapy by regulating the expression DNA repair proteins. Examination of 211 lung cancer tissue samples revealed that eIF3a expression negatively correlates with responses of the patients to cisplatin treatment. Ectopic over-expression or knockdown of eIF3a reduced or increased cellular resistance, respectively, to cisplatin, doxorubicine, and etoposide (VP-16) in cell lines as determined using MTT assay. Altering eIF3a expression also changed DNA repair activity as well as the expression of DNA repair proteins. We conclude that eIF3a possibly suppresses the synthesis of DNA repair proteins via translational control, which in turn contributes to the increased sensitivity to DNA-damaging anticancer drugs. 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 1749. doi:10.1158/1538-7445.AM2011-1749