Abstract 1504: Inhibition of RNA-dependent protein kinase (PKR) enhances radiation sensitivity in lung cancer cells

Abstract

Abstract We have previously demonstrated that radiation resistance in MEFs is mediated in part through RNA-dependent protein kinase (PKR) possibly through upregulation of AKT and NFk-B. The role of PKR in cancer cells has not been evaluated. In this study, we show that the transduction of MEFs and lung cancer cells with adenoviral wt PKR results in nuclear translocation of PKR, activation of AKT1/2 and increased radiation resistance. The transduction of lung cancer cells or MEFs with a dominant negative adenoviral PKR vector blocks nuclear translocation of PKR, inhibits AKT activation and leads to the reversal of radiation resistance. Plasmid transduction of MEFs and lung cancer cells with nuclear targeted wt PKR vectors also results in AKT1/2 activation and increased radiation resistance. This effect is selectively abrogated by plasmid transduction of dominant negative PKR vectors which inhibit AKT1/2 activation and restore radiation sensitivity. These findings suggest a novel role for PKR in lung cancer cells as a mediator of radiation resistance possibly through translocation of the protein product to the nucleus and activation of AKT1/2. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1504.