Abstract
Abstract The transcription factor NF-E2-related factor 2 (NRF2) plays a critical role in cellular defense system by up-regulating multiple antioxidant genes. Therefore, the identification of biomarker genes reflecting NRF2 activity would be important for the prediction of high-risk populations to environmental stresses. In the current study, we have investigated human genes of which expression is highly dependent on NRF2 to establish biomarker genes for NRF2 activity. For this purpose, NRF2-specific interfering RNA was stably introduced in normal human renal epithelial cells (HK-2) and human bronchial epithelial cells (NL-20), and changes in inducible genes were determined following treatment with 4 types of NRF2 activators: thiol-reacting sulforaphane, free-radical generating tert-butylhydroquinone, Michael acceptor cinnamic aldehyde and pro-oxidant hydrogen peroxide. These treatments showed relatively common alterations in gene expression, and among these, the expression of aldoketo reductase (AKR) 1C1 was highly inducible by all of these treatments in an NRF2-depedent manner. The levels for AKRs were found to be constitutively high in renal carcinoma A498 cells, of which NRF2 activity is elevated compared to normal renal epithelial HK-2 cells. In addition, the expression of AKRs was greatly enhanced by NRF2 activator treatments in human monocytes (U937), implying the potential utility of AKRs as a peripheral NRF2 marker. In conclusion, our results indicate that the expression of AKRs is highly dependent on NRF2 in human cells; therefore AKRs can be an effective biomarker for predicting NRF2 activity in human cells. 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 2066. doi:1538-7445.AM2012-2066
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