p38α MAPK is required for arsenic-induced cell transformation
Arsenic exposure has been reported to cause neoplastic transformation through the activation of PcG proteins. In the present study, we show that activation of p38α mitogen‐activated protein kinase (MAPK) is required for arsenic‐induced neoplastic transformation. Exposure of cells to 0.5 μM arsenic i...
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Published in | Molecular carcinogenesis Vol. 55; no. 5; pp. 910 - 917 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
Blackwell Publishing Ltd
01.05.2016
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Subjects | |
Online Access | Get full text |
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Summary: | Arsenic exposure has been reported to cause neoplastic transformation through the activation of PcG proteins. In the present study, we show that activation of p38α mitogen‐activated protein kinase (MAPK) is required for arsenic‐induced neoplastic transformation. Exposure of cells to 0.5 μM arsenic increased CRE and c‐Fos promoter activities that were accompanied by increases in p38α MAPK and CREB phosphorylation and expression levels concurrently with AP‐1 activation. Introduction of short hairpin (sh) RNA‐p38α into BALB/c 3T3 cells markedly suppressed arsenic‐induced colony formation compared with wildtype cells. CREB phosphorylation and AP‐1 activation were decreased in p38α knockdown cells after arsenic treatment. Arsenic‐induced AP‐1 activation, measured as c‐Fos and CRE promoter activities, and CREB phosphorylation were attenuated by p38 inhibition in BALB/c 3T3 cells. Thus, p38α MAPK activation is required for arsenic‐induced neoplastic transformation mediated through CREB phosphorylation and AP‐1 activation. © 2015 Wiley Periodicals, Inc. |
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Bibliography: | ArticleID:MC22331 istex:BCBC884C30A7928DCBADA0F2B56A8EA5E8E4F366 ark:/67375/WNG-0XT62PK8-V Hormel Foundation - No. ES106548 National Institutes of Health - No. CA172457 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0899-1987 1098-2744 |
DOI: | 10.1002/mc.22331 |