Identification of molecular candidates and interaction networks via integrative toxicogenomic analysis in a human cell line following low-dose exposure to the carcinogenic metals cadmium and nickel

  • Authors:
    • Jee Young Kwon
    • Jong-Il Weon
    • Preeyaporn Koedrith
    • Kang-Sik Park
    • Im Soon Kim
    • Young Rok Seo
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  • Published online on: July 4, 2013     https://doi.org/10.3892/or.2013.2587
  • Pages: 1185-1194
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Abstract

Cadmium and nickel have been classified as carcinogenic to humans by the World Health Organization's International Agency for Research on Cancer. Given their prevalence in the environment, the fact that cadmium and nickel may cause diseases including cancer even at low doses is a cause for concern. However, the exact mechanisms underlying the toxicological effects induced by low-dose exposure to cadmium and nickel remain to be elucidated. Furthermore, it has recently been recognized that integrative analysis of DNA, mRNA and proteins is required to discover biomarkers and signaling networks relevant to human toxicant exposure. In the present study, we examined the deleterious effects of chronic low-dose exposure of either cadmium or nickel on global profiling of DNA copy number variation, mRNA and proteins. Array comparative genomic hybridization, gene expression microarray and functional proteomics were conducted, and a bioinformatics tool, which predicted signaling pathways, was applied to integrate data for each heavy metal separately and together. We found distinctive signaling networks associated with subchronic low-dose exposure to cadmium and nickel, and identified pathways common to both. ACTB, HSP90AA1, HSPA5 and HSPA8, which are key mediators of pathways related to apoptosis, proliferation and neoplastic processes, were key mediators of the same pathways in low-dose nickel and cadmium exposure in particular. CASP-associated signaling pathways involving CASP3, CASP7 and CASP9 were observed in cadmium-exposed cells. We found that HSP90AA1, one of the main modulators, interacted with HIF1A, AR and BCL2 in nickel-exposed cells. Interestingly, we found that HSP90AA1 was involved in the BCL2-associated apoptotic pathway in the nickel-only data, whereas this gene interacted with several genes functioning in CASP-associated apoptotic signaling in the cadmium-only data. Additionally, JUN and FASN were main modulators in nickel-responsive signaling pathways. Our results provide valuable biomarkers and distinctive signaling networks that responded to subchronic low-dose exposure to cadmium and nickel.
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September 2013
Volume 30 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Kwon JY, Weon J, Koedrith P, Park K, Kim IS and Seo YR: Identification of molecular candidates and interaction networks via integrative toxicogenomic analysis in a human cell line following low-dose exposure to the carcinogenic metals cadmium and nickel. Oncol Rep 30: 1185-1194, 2013.
APA
Kwon, J.Y., Weon, J., Koedrith, P., Park, K., Kim, I.S., & Seo, Y.R. (2013). Identification of molecular candidates and interaction networks via integrative toxicogenomic analysis in a human cell line following low-dose exposure to the carcinogenic metals cadmium and nickel. Oncology Reports, 30, 1185-1194. https://doi.org/10.3892/or.2013.2587
MLA
Kwon, J. Y., Weon, J., Koedrith, P., Park, K., Kim, I. S., Seo, Y. R."Identification of molecular candidates and interaction networks via integrative toxicogenomic analysis in a human cell line following low-dose exposure to the carcinogenic metals cadmium and nickel". Oncology Reports 30.3 (2013): 1185-1194.
Chicago
Kwon, J. Y., Weon, J., Koedrith, P., Park, K., Kim, I. S., Seo, Y. R."Identification of molecular candidates and interaction networks via integrative toxicogenomic analysis in a human cell line following low-dose exposure to the carcinogenic metals cadmium and nickel". Oncology Reports 30, no. 3 (2013): 1185-1194. https://doi.org/10.3892/or.2013.2587