Carcinogenic nickel induces genes involved with hypoxic stress
Autor: | K, Salnikow, M V, Blagosklonny, H, Ryan, R, Johnson, M, Costa |
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Rok vydání: | 2000 |
Předmět: |
Mice
Knockout Ionophores Blotting Western Intracellular Signaling Peptides and Proteins Gene Expression Nuclear Proteins Proteins Cell Cycle Proteins Fibroblasts Blotting Northern Hypoxia-Inducible Factor 1 alpha Subunit Cell Hypoxia DNA-Binding Proteins Mice Nickel Carcinogens Tumor Cells Cultured Animals Humans Calcium Hypoxia-Inducible Factor 1 RNA Messenger RNA Processing Post-Transcriptional Signal Transduction Transcription Factors |
Zdroj: | Cancer research. 60(1) |
ISSN: | 0008-5472 |
Popis: | 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. |
Databáze: | OpenAIRE |
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