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Review
. 2013 Sep 12:4:246.
doi: 10.3389/fphys.2013.00246.

Overview on how oncogenic Kras promotes pancreatic carcinogenesis by inducing low intracellular ROS levels

Bo Kong  1 , Chengjia Qia, Mert Erkan, Jörg Kleeff, Christoph W Michalski
Affiliations
Review

Overview on how oncogenic Kras promotes pancreatic carcinogenesis by inducing low intracellular ROS levels

Bo Kong et al. Front Physiol. .

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease without clearly known disease causes. Recent epidemiological and animal studies suggest that the supplementation of dietary antioxidants (e.g., vitamins C and E) decreases cancer risk, implying that increased reactive oxygen species (ROS) may play a role in pancreatic carcinogenesis. However, oncogenic Kras mutations (e.g., Kras(G12D)), which are present in more than 90% of PDAC, have been proven to foster low intracellular ROS levels. Here, oncogenic Kras activates expression of a series of anti-oxidant genes via Nrf2 (nuclear factor, erythroid derived 2, like 2) and also mediates an unusual metabolic pathway of glutamine to generate NADPH. This can then be used as the reducing power for ROS detoxification, leading collectively to low ROS levels in pancreatic pre-neoplastic cells and in cancer cells. In adult stem cells and cancer stem cells, low ROS levels have been associated with the formation of a proliferation-permissive intracellular environment and with perseverance of self-renewal capacities. Therefore, it is conceivable that low intracellular ROS levels may contribute significantly to oncogenic Kras-mediated PDAC formation.

Keywords: KrasG12D; oncogenic Kras; pancreatic cancer; pancreatic cancer stem cells; reactive oxygen species; redox equilibrium.

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Figures

Figure 1
Figure 1
Schema showing how oncogenic Kras induces low intracellular ROS levels.
See this image and copyright information in PMC

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