Title: Carcinogenic nickel induces genes involved with hypoxic stress.
Authors: Salnikow, K; Blagosklonny, M V; Ryan, H; Johnson, R; Costa, M
Published In Cancer Res, (2000 Jan 1)
Abstract: Carcinogenic nickel compounds alter the program of gene expression in normal cells and induce a pattern of gene expression similar to that found in nickel-induced cancers. Here we have demonstrated that nickel exposure induced hypoxic signaling pathways by inducing hypoxia-inducible transcription factor-1 (HIF-1), which mediated the induction of genes required by cells to survive hypoxia. We also show that a new gene, Cap43, is dependent upon HIF-1 because only HIF-1-proficient cells induced Cap43 when exposed to either hypoxia or nickel. We also show that glyceraldehyde-3-phosphate dehydrogenase, a gene induced by hypoxia through HIF-1, was similar to Cap43 in that it required HIF-1-proficient cells to be induced by either nickel or hypoxia. These data demonstrate that nickel exposure turns on signaling for hypoxic stress, which may be important in its carcinogenesis.
PubMed ID: 10646848
MeSH Terms: Animals; Blotting, Northern; Blotting, Western; Calcium/metabolism; Carcinogens/toxicity*; Cell Cycle Proteins; Cell Hypoxia/genetics*; Cell Hypoxia/physiology; DNA-Binding Proteins/genetics; DNA-Binding Proteins/physiology*; Fibroblasts/metabolism; Gene Expression/drug effects*; Humans; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Intracellular Signaling Peptides and Proteins; Ionophores/pharmacology; Mice; Mice, Knockout; Nickel/toxicity*; Nuclear Proteins/genetics; Nuclear Proteins/physiology*; Proteins/drug effects*; Proteins/metabolism; RNA Processing, Post-Transcriptional; RNA, Messenger/metabolism; Signal Transduction/drug effects; Transcription Factors*; Tumor Cells, Cultured