Nickel compounds induce apoptosis in human bronchial epithelial Beas-2B cells by activation of c-Myc through ERK pathway.
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.
Li
Qin
Q
New York University School of Medicine, Nelson Institute of Environmental Medicine, 57 Old Forge Road, NY 10987, USA.
Suen
Ting-Chung
TC
Sun
Hong
H
Arita
Adriana
A
Costa
Max
M
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D005434:Flow Cytometry; D017930:Genes, Reporter; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D008156:Luciferases / Q000378:metabolism; D009532:Nickel / Q000633:toxicity*; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D018631:ras Proteins / Q000235:genetics / Q000502:physiology
D016271:Proto-Oncogene Proteins c-myc; D012313:RNA; D009532:Nickel; D008156:Luciferases; D048049:Extracellular Signal-Regulated MAP Kinases; D018631:ras Proteins