| Regulation of pancreatic cancer growth by superoxide. | |
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MedLine Citation:
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PMID: 22392697 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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K-ras mutations have been identified in up to 95% of pancreatic cancers, implying their critical role in the molecular pathogenesis. Expression of K-ras oncogene in an immortalized human pancreatic ductal epithelial cell line, originally derived from normal pancreas (H6c7), induced the formation of carcinoma in mice. We hypothesized that K-ras oncogene correlates with increased non-mitochondrial-generated superoxide (O 2.-), which could be involved in regulating cell growth contributing to tumor progression. In the H6c7 cell line and its derivatives, H6c7er-Kras+ (H6c7 cells expressing K-ras oncogene), and H6c7eR-KrasT (tumorigenic H6c7 cells expressing K-ras oncogene), there was an increase in hydroethidine fluorescence in cell lines that express K-ras. Western blots and activity assays for the antioxidant enzymes that detoxify O 2.- were similar in these cell lines suggesting that the increase in hydroethidine fluorescence was not due to decreased antioxidant capacity. To determine a possible non-mitochondrial source of the increased levels of O 2.-, Western analysis demonstrated the absence of NADPH oxidase-2 (NOX2) in H6c7 cells but present in the H6c7 cell lines expressing K-ras and other pancreatic cancer cell lines. Inhibition of NOX2 decreased hydroethidine fluorescence and clonogenic survival. Furthermore, in the cell lines with the K-ras oncogene, overexpression of superoxide dismutases that detoxify non-mitochondrial sources of O 2.-, and treatment with the small molecule O 2.- scavenger Tempol, also decreased hydroethidine fluorescence, inhibited clonogenic survival and inhibited growth of tumor xenografts. Thus, O 2.- produced by NOX2 in pancreatic cancer cells with K-ras, may regulate pancreatic cancer cell growth. © 2012 Wiley Periodicals, Inc. |
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Authors:
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Juan Du; Elke S Nelson; Andrean L Simons; Kristen E Olney; Justin C Moser; Hannah E Schrock; Brett A Wagner; Garry R Buettner; Brian J Smith; Melissa L T Teoh; Ming-Sound Tsao; Joseph J Cullen |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-3-5 |
Journal Detail:
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Title: Molecular carcinogenesis Volume: - ISSN: 1098-2744 ISO Abbreviation: - Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-3-6 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8811105 Medline TA: Mol Carcinog Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 Wiley Periodicals, Inc. |
Affiliation:
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Departments of Radiation Oncology, University of Iowa College of Medicine, Iowa City, Iowa. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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