Abstract
Abstract Type 2 papillary renal cell carcinoma (PRCC2) is an aggressive subtype of kidney cancer that has no known effective treatment modality. The hereditary form of the tumor is known to associate with the loss of fumarate hydratase (FH) gene function. However, FH gene mutation has yet to be found in sporadic PRCC2. Herein, we report the overexpression of antioxidant response element (ARE) controlled genes as a common feature that is shared between the hereditary and sporadic form of PRCC2. We demonstrate that fumarate stabilizes NRF1 and NRF2, which drive the upregulation of ARE controlled genes. We propose that fumarate stabilizes NRF1 and NRF2 through direct suppression of KEAP1. This finding better explains the phenotypical differences that are apparent between PRCC2 and CCRCC and may lead to the development of an effective therapeutic against PRCC2. 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 3820. doi:10.1158/1538-7445.AM2011-3820
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