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

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 (R...

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Main Authors:	Kong, Bo, Qia, Chengjia, Erkan, Mert, Kleeff, Jörg, Michalski, Christoph W.
Format:	Online
Language:	English
Published:	Frontiers Media S.A. 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3771311/

id	pubmed-3771311
recordtype	oai_dc
spelling	pubmed-37713112013-09-23 Overview on how oncogenic Kras promotes pancreatic carcinogenesis by inducing low intracellular ROS levels Kong, Bo Qia, Chengjia Erkan, Mert Kleeff, Jörg Michalski, Christoph W. Physiology 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., KrasG12D), 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. Frontiers Media S.A. 2013-09-12 /pmc/articles/PMC3771311/ /pubmed/24062691 http://dx.doi.org/10.3389/fphys.2013.00246 Text en Copyright © 2013 Kong, Qia, Erkan, Kleeff and Michalski. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Kong, Bo Qia, Chengjia Erkan, Mert Kleeff, Jörg Michalski, Christoph W.
spellingShingle	Kong, Bo Qia, Chengjia Erkan, Mert Kleeff, Jörg Michalski, Christoph W. Overview on how oncogenic Kras promotes pancreatic carcinogenesis by inducing low intracellular ROS levels
author_facet	Kong, Bo Qia, Chengjia Erkan, Mert Kleeff, Jörg Michalski, Christoph W.
author_sort	Kong, Bo
title	Overview on how oncogenic Kras promotes pancreatic carcinogenesis by inducing low intracellular ROS levels
title_short	Overview on how oncogenic Kras promotes pancreatic carcinogenesis by inducing low intracellular ROS levels
title_full	Overview on how oncogenic Kras promotes pancreatic carcinogenesis by inducing low intracellular ROS levels
title_fullStr	Overview on how oncogenic Kras promotes pancreatic carcinogenesis by inducing low intracellular ROS levels
title_full_unstemmed	Overview on how oncogenic Kras promotes pancreatic carcinogenesis by inducing low intracellular ROS levels
title_sort	overview on how oncogenic kras promotes pancreatic carcinogenesis by inducing low intracellular ros levels
description	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., KrasG12D), 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.
publisher	Frontiers Media S.A.
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3771311/
_version_	1612011161139544064

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

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