p38α MAPK is required for arsenic-induced cell transformation

Hong Gyum Kim, Chengcheng Shi, Ann M. Bode, Zigang Dong

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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 0.5μM 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.

Original languageEnglish (US)
Pages (from-to)910-917
Number of pages8
JournalMolecular Carcinogenesis
Volume55
Issue number5
DOIs
StatePublished - May 1 2016

Bibliographical note

Funding Information:
This work was supported by The Hormel Foundation and National Institutes of Health grants ES106548 and CA172457. Grant sponsor: Hormel Foundation; Grant number: ES106548; Grant sponsor: National Institutes of Health; Grant number: CA172457

Publisher Copyright:
© 2016 Wiley Periodicals, Inc.

Keywords

  • AP-1
  • Arsenic
  • CREB
  • Cell transformation
  • P38α

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