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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Nickel compounds induce apoptosis in human bronchial epithelial Beas-2B cells by activation of c-Myc through ERK pathway.

Authors: Li, Qin; Suen, Ting-Chung; Sun, Hong; Arita, Adriana; Costa, Max

Published In Toxicol Appl Pharmacol, (2009 Mar 1)

Abstract: Nickel compounds are carcinogenic to humans and have been shown to alter epigenetic homeostasis. The c-Myc protein controls 15% of human genes and it has been shown that fluctuations of c-Myc protein alter global epigenetic marks. Therefore, the regulation of c-Myc by nickel ions in immortalized but not tumorigenic human bronchial epithelial Beas-2B cells was examined in this study. It was found that c-Myc protein expression was increased by nickel ions in non-tumorigenic Beas-2B and human keratinocyte HaCaT cells. The results also indicated that nickel ions induced apoptosis in Beas-2B cells. Knockout of c-Myc and its restoration in a rat cell system confirmed the essential role of c-Myc in nickel ion-induced apoptosis. Further studies in Beas-2B cells showed that nickel ion increased the c-Myc mRNA level and c-Myc promoter activity, but did not increase c-Myc mRNA and protein stability. Moreover, nickel ion upregulated c-Myc in Beas-2B cells through the MEK/ERK pathway. Collectively, the results demonstrate that c-Myc induction by nickel ions occurs via an ERK-dependent pathway and plays a crucial role in nickel-induced apoptosis in Beas-2B cells.

PubMed ID: 19135467 Exiting the NIEHS site

MeSH Terms: Apoptosis/drug effects*; Blotting, Western; Cell Line; Epithelial Cells/drug effects*; Extracellular Signal-Regulated MAP Kinases/physiology*; Flow Cytometry; Genes, Reporter; Humans; Keratinocytes/drug effects; Luciferases/metabolism; Nickel/toxicity*; Proto-Oncogene Proteins c-myc/physiology*; RNA/biosynthesis; RNA/genetics; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction/drug effects; ras Proteins/genetics; ras Proteins/physiology

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