title: p38α MAPK is required for arsenic-induced cell transformation.
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 0.5 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.
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota.
authors.forename: Hong-Gyum
authors.initials: HG
authors.lastname: Kim
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota.|The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Shi
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota.
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D041702:BALB 3T3 Cells; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D051379:Mice; D048308:Mitogen-Activated Protein Kinase 14 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D018808:Transcription Factor AP-1; D048308:Mitogen-Activated Protein Kinase 14; D001151:Arsenic
keywords: AP-1; CREB; arsenic; cell transformation; p38α