GeneChip analysis of signaling pathways effected by nickel
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Published on: July 20, 2019
Konstantin Salnikow1, Todd Davidson, Thomas Kluz
1Nelson Institute of Environmental Medicine, NYU/NIEHS Center of Excellence, The NYU Cancer Institute, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA. salnikow@env.med.nyu.edu
Abstract:
The carcinogenicity of nickel compounds has been shown in numerous epidemiological and animal studies. Carcinogenesis is generally considered as a multistep accumulation of genetic alterations. Nickel, however, being highly carcinogenic is only a weak mutagen. We hypothesize that nickel may act by modulating signaling pathways, and subsequently by reprogramming transcription factors. Insoluble nickel is considered to be more carcinogenic than soluble. In this study using GeneChip technology we compared changes in gene expression caused by soluble and insoluble nickel compounds. We found that both soluble and insoluble nickel compounds induce similar signaling pathways following 20 h of in vitro exposure. For example, both nickel compounds activated a number of transcription factors including hypoxia-inducible factor I (HIF-1) and p53. The induction of these important transcription factors exerts potent selective pressure leading to cell transformation. The obtained data are in agreement with our previous observations that acute nickel exposure activates HIF-1 and p53 transcription factors and in nickel-transformed cells, the ratio of HIF-I activity to p53 activity was shifted towards high HIF-I activity. The activation of the same signaling pathways by soluble and insoluble nickel compounds suggested that both nickel compounds have similar carcinogenic potential in vitro.
Insights
Nickel compounds are carcinogenic but weak mutagens. This study shows both soluble and insoluble nickel activate similar cell signaling pathways, including hypoxia-inducible factor I (HIF-1) and p53, suggesting similar in vitro carcinogenic potential.
Area of Science:
- Environmental toxicology
- Molecular carcinogenesis
Background:
- Nickel compounds are known carcinogens, yet their mechanism is unclear as they are weak mutagens.
- Carcinogenesis is typically a multistep process involving genetic alterations.
- Nickel's carcinogenic potential may involve modulating signaling pathways and transcription factors.
Purpose of the Study:
- To investigate the gene expression changes induced by soluble and insoluble nickel compounds in vitro.
- To compare the signaling pathways affected by different forms of nickel exposure.
- To understand the role of nickel in reprogramming transcription factors during carcinogenesis.
Main Methods:
- Utilized GeneChip technology to analyze gene expression profiles.
- Exposed cells in vitro to both soluble and insoluble nickel compounds.
- Measured the activation of key transcription factors, including HIF-1 and p53.
Main Results:
- Both soluble and insoluble nickel compounds induced similar signaling pathways after 20 hours of in vitro exposure.
- Activation of transcription factors hypoxia-inducible factor I (HIF-1) and p53 was observed for both nickel forms.
- Data align with previous findings showing acute nickel exposure activates HIF-1 and p53, with a shift towards HIF-1 activity in transformed cells.
Conclusions:
- The activation of common signaling pathways by soluble and insoluble nickel suggests similar in vitro carcinogenic potential.
- Nickel may exert its carcinogenic effects by reprogramming transcription factors through signaling pathway modulation.
- Further research into nickel's role in cell transformation and the balance of HIF-1 and p53 activity is warranted.
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