Arsenic mediates cell proliferation and gene expression in the bladder epithelium: association with activating protein-1 transactivation
| Autor: | P P, Simeonova, S, Wang, W, Toriuma, V, Kommineni, J, Matheson, N, Unimye, F, Kayama, D, Harki, M, Ding, V, Vallyathan, M I, Luster |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Transcriptional Activation Arsenites Urinary Bladder Mice Transgenic Immediate-Early Proteins Mice Genes jun Animals Humans Tissue Distribution Luciferases Crosses Genetic Early Growth Response Protein 1 Hyperplasia Intracellular Signaling Peptides and Proteins Genes fos Proteins Sodium Compounds DNA-Binding Proteins Mice Inbred C57BL Transcription Factor AP-1 Gene Expression Regulation Mice Inbred DBA CCAAT-Enhancer-Binding Proteins Arsenates Tetradecanoylphorbol Acetate Female Urothelium Cell Division Transcription Factor CHOP DNA Damage Transcription Factors |
| Zdroj: | Cancer research. 60(13) |
| ISSN: | 0008-5472 |
| Popis: | Although the mechanism of action has not yet been defined, epidemiological studies have demonstrated an association between elevated arsenic levels in drinking water and the incidence of urinary bladder transitional cell carcinomas. In the current studies, we demonstrate that mice exposed to 0.01% sodium arsenite in drinking water develop hyperplasia of the bladder urothelium within 4 weeks of exposure. This was accompanied by the accumulation of inorganic trivalent arsenic, and to a lesser extent dimethylarsinic acid, in bladder tissue, as well as a persistent increase in DNA binding of the activating protein (AP)-1 transcription factor. AP-1 transactivation by arsenic also occurred in bladders of transgenic mice containing an AP-1 luciferase reporter. Consistent with these in vivo observations, arsenite increased cell proliferation and AP-1 DNA binding in a human bladder epithelial cell line. Gene expression studies using RNase protection assays, reverse transcription-PCR, and cDNA microarrays indicated that arsenite alters the expression of a number of genes associated with cell growth, such as c-fos, c-jun, and EGR-1, as well as cell arrest, such as GADD153 and GADD45. The proliferation-enhancing effect of arsenic on uroepithelial cells likely contributes to its ability to cause cancer. |
| Databáze: | OpenAIRE |
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