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Molecular biology of nickel carcinogenesis: Identification of differentially expressed genes in morphologically transformed C3H10T1/2 Cl 8 mouse embryo fibroblast cell lines induced by pecific insoluble nickel compounds

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Abstract

Inhalation of mixtures of insoluble and soluble nickel compounds by humans during nickel refining has been associated with excess lung and nasal sinus cancers. Insoluble nickel subsulfide (Ni3S2) and nickel oxide (NiO) are carcinogenic to rodents by inhalation. We previously showed that insoluble Ni3S2, crystalline nickel monosulfide (NiS), and green (high temperature, HT) and black (low temperature, LT) NiO, induced morphological transformation in cultured C3H/10T1/2 Cl 8 (10T1/2) mouse embryo cells. To understand molecular mechanisms of carcinogenesis by insoluble nickel compounds, we used random, arbitrarily primed-polymerase chain reaction (RAP-PCR) mRNA differential display and identified nine cDNA fragments that were differentially expressed between nontransformed and nickel-transformed cell lines in ~ 10.0% of the total mRNA. Expression of the calnexin gene (encoding a type I membrane protein/molecular chaperone), the ect-2 proto-oncogene, and the stress-inducible gene, Wdr1, was upregulated. Expression of six genes – the vitamin D interacting protein/thyroid hormone activating protein 80 (DRIP/TRAP-80) gene, the insulin-like growth factor receptor 1 (IGFR1) gene, the small nuclear activating protein (SNAP C3) gene, and three unknown genes, was down-regulated, in nickel-transformed cell lines. We hypothesize that these resulting aberrations in gene expression could contribute to the induction and/or maintenance of morphological transformation induced by specific insoluble nickel compounds.

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Authors and Affiliations

  1. Department of Molecular Microbiology and Immunology and USC/Norris Comprehensive Cancer Center Keck School of Medicine, University of Southern California, Los Angeles, CA, 90089, USA

    Rini Verma, Jamuna Ramnath, Farrah Clemens & Lisa C. Kaspin

  2. Department of Molecular Microbiology and Immunology, Department of Pathology, USC/Norris Comprehensive Cancer Center Keck School of Medicine, USA

    Joseph R. Landolph

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  1. Rini Verma
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  2. Jamuna Ramnath
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  3. Farrah Clemens
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  4. Lisa C. Kaspin
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  5. Joseph R. Landolph
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Correspondence to Joseph R. Landolph.

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Verma, R., Ramnath, J., Clemens, F. et al. Molecular biology of nickel carcinogenesis: Identification of differentially expressed genes in morphologically transformed C3H10T1/2 Cl 8 mouse embryo fibroblast cell lines induced by pecific insoluble nickel compounds. Mol Cell Biochem 255, 203–216 (2004). https://doi.org/10.1023/B:MCBI.0000007276.94488.3d

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