Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis

Gina M. DeNicola, Florian A. Karreth, Timothy J. Humpton, Aarthi Gopinathan, Cong Wei, Kristopher Frese, Dipti Mangal, Kenneth H. Yu, Charles J. Yeo, Eric S. Calhoun, Francesca Scrimieri, Jordan M. Winter, Ralph H. Hruban, Christine Iacobuzio-Donahue, Scott E. Kern, Ian A. Blair and David A. Tuveson ()
Additional contact information
Gina M. DeNicola: Li Ka Shing Centre, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge CB2 0RE, UK
Florian A. Karreth: Li Ka Shing Centre, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge CB2 0RE, UK
Timothy J. Humpton: Li Ka Shing Centre, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge CB2 0RE, UK
Aarthi Gopinathan: Li Ka Shing Centre, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge CB2 0RE, UK
Cong Wei: Center for Cancer Pharmacology, University of Pennsylvania
Kristopher Frese: Li Ka Shing Centre, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge CB2 0RE, UK
Dipti Mangal: Center for Cancer Pharmacology, University of Pennsylvania
Kenneth H. Yu: Center for Cancer Pharmacology, University of Pennsylvania
Charles J. Yeo: Jefferson Medical College
Eric S. Calhoun: Alma College
Francesca Scrimieri: The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins Medical Institutions
Jordan M. Winter: The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins Medical Institutions
Ralph H. Hruban: The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins Medical Institutions
Christine Iacobuzio-Donahue: The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins Medical Institutions
Scott E. Kern: The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins Medical Institutions
Ian A. Blair: Center for Cancer Pharmacology, University of Pennsylvania
David A. Tuveson: Li Ka Shing Centre, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge CB2 0RE, UK

Nature, 2011, vol. 475, issue 7354, 106-109

Abstract: Radical role reversal Reactive oxygen species (ROS), such as free radicals, are mutagenic and might therefore be expected to promote tumorigenesis. However, this work shows that expression of the oncogenes Kras, Braf and Myc at endogenous levels in mouse cells in fact reduces ROS levels. Some oncogenes are also shown to induce the transcription factor Nrf2, which acts to detoxify ROS. In line with this finding, deletion of Nrf2 impairs K-Ras-induced pancreatic tumour formation. Modulation of the redox state in cells thus seems to be an important factor in determining tumorigenic potential, and may be a possible target for therapy.

Date: 2011
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DOI: 10.1038/nature10189

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