p38α MAPK is required for arsenic-induced cell transformation

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

Research output: Contribution to journalArticle

7 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

Keywords

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

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