The role of hypoxia-inducible signaling pathway in nickel carcinogenesis.

Salnikow, Konstantin; Davidson, Thomas; Costa, Max

doi:10.1289/ehp.02110s5831

Cited by 112 publications

(106 citation statements)

References 22 publications

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“…These data support our previous findings that NDRG1 expression is induced by HIF-1α in human tumor cells (8). In addition, the HIF-1α expression precedes NDRG1 expression, indicating that it may be a prerequisite for NDRG1 upregulation since it is its major transcriptional regulator (8,21,45,46). The same holds true for other HIF-1α-regulated genes such as CA9 (47).…”

Section: Discussionsupporting

confidence: 90%

Time- and oxygen-dependent expression and regulation of NDRG1 in human brain cancer cells

et al. 2017

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Abstract. N-myc downstream-regulated gene 1 (NDRG1) is a tumor suppressor with the potential to suppress metastasis, invasion and migration of cancer cells. It is regulated under stress conditions such as starvation or hypoxia. NDRG1 regulation is both induced and controlled by HIF-1α-dependent and -independent pathways under hypoxic conditions. However, there are profound differences in the way NDRG1 expression is regulated by HIF-1α and other transcription factors. Therefore, we aimed to define the time-dependent pattern of NDRG1 mRNA and protein expression in human glioblastoma cell lines in extreme hypoxia and after re-oxygenation as well as under normoxic conditions. Furthermore, we ascribe the regulation of NDRG1 to the transcription factors HIF-1α, SP1, CEBPα, YB-1 and Smad7 in a time-dependent manner. The human malignant glioma cell lines U87-MG, U373 and GaMG were cultured for 1, 6 and 24 h under hypoxic (0.1% O 2 ) conditions and then they were re-oxygenated. The mRNA expression of NDRG1, HIF-1α SP1, CEBPα, YB-1 and Smad7 was measured using semi-quantitative RT-PCR analysis. Their protein expression was analyzed using western blotting. Our experiments revealed that long-term (24 h), but not short-term hypoxia led to the induction of NDRG1 expression in human glioma cell lines. NDRG1 expression was found to correlate with the protein expression of HIF-1α, SP1, CEBPα, YB-1 and Smad7. The present study suggests for the first time that SP1 regulates NDRG1 expression in glioma cells under hypoxia in a time-dependent manner along with HIF-1α, CEBPα, YB-1 and Smad7. These molecules, each separately or in combination, may possess the potential to become target molecules for antitumor therapeutic approaches particularly in human brain tumors.

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Section: Discussionsupporting

confidence: 90%

Time- and oxygen-dependent expression and regulation of NDRG1 in human brain cancer cells

et al. 2017

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“…Similar stress-response molecular mechanisms have been reported to occur during tumor progression and in other models of cell toxicity in vitro (Salnikow et al 2002;Bando et al 2003;Luhe et al 2003;Fei et al 2004;Erler et al 2006;Hatzivassiliou et al 2005;Kanzawa et al 2005;Burton et al 2006). These findings suggest the possible involvement of hypoxia-related transcriptional activation in general cell survival strategies.…”

Section: Discussionsupporting

confidence: 69%

Hypoxia‐like transcriptional activation in TMT‐induced degeneration: microarray expression analysis on PC12 cells

Lattanzi¹,

Bernardini²,

Gangitano³

et al. 2006

Journal of Neurochemistry

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To more clearly elucidate the complete network of molecular mechanisms induced by trimethyltin (TMT) toxicity, we used a homogeneous cell culture model represented by PC12 cells treated with 1 and 5 lmol/L TMT for 24 h. The gene expression profile was performed by microarray analysis, enabling us to identify 189 genes that were significantly modulated in treated cells, compared with controls. The main effects of TMT on gene expression seem to be related to the activation of metabolic processes (glycolysis and lipogenesis) along with cell death pathways, membrane remodeling and intracellular biomolecules trafficking. These alterations are triggered by the neurotoxicant earlier than a strong decrease in cell viability, which occurs at higher TMT concentrations or at later time points. Some aspects of the transcriptional modulation observed in this study resemble the gene activation known to occur during cell response to hypoxia. Other cell toxicants have also been reported to exert similar effects on gene expression. Therefore, our data help to delineate general basic adaptive mechanisms possibly shared by cells responding to different death-inducing noxae, such as TMT.

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“…These studies used VHL-deficient renal carcinoma cell lines with ectopic expression of VHL (24)(25)(26)(27) or forced expression of HIF-1a and HIF-2a (26,28) or by comparing gene expression from HIF-1a knockout cells to control cells (29,30).…”

Section: Introductionmentioning

confidence: 99%

Role of ETS Transcription Factors in the Hypoxia-Inducible Factor-2 Target Gene Selection

et al. 2006

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Tumor hypoxia often directly correlates with aggressive phenotype, metastasis progression, and resistance to chemotherapy. Two transcription factors [hypoxia-inducible factor-1A (HIF-1A) and HIF-2A] are dramatically induced in hypoxic areas and regulate the expression of genes necessary for tumor adaptation to the conditions of low oxygen; however, the relative contribution of these factors is controversial. We used RNA interference-mediated inactivation of HIF-1A or HIF-2A followed by microarray analysis to identify genes specifically regulated by either HIF-1 or HIF-2 in hypoxia. We found that, in the MCF7 cell line, the vast majority of hypoxiaresponsive genes (>80%) were dependent on the presence of HIF-1A. However, a small group of genes were preferentially regulated by HIF-2A. Promoter analysis for this group of genes revealed that all of them have putative binding sites for ETS family transcription factors, and 10 of 11 HIF-2A-dependent genes had at least one potential hypoxia-responsive element (HRE) in proximity to an ETS transcription factor binding site. Knockdown of ELK-1, the most often represented member of ETS family, significantly reduced hypoxic induction of the HIF-2A-dependent genes. Physical and functional interaction between ELK-1 and HIF-2A were supported by coimmunoprecipitation of these two proteins, luciferase reporter assay using CITED2 promoter, and binding of ELK-1 protein to the promoters of CITED2 and WISP2 genes in proximity to a HRE. These data suggest that the choice of the target genes by HIF-1 or HIF-2 depends on availability and cooperation of HIFs with other factors recognizing their cognate elements in the promoters. (Cancer Res 2006; 66(11): 5641-7)

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The role of hypoxia-inducible signaling pathway in nickel carcinogenesis.

Cited by 112 publications

References 22 publications

Time- and oxygen-dependent expression and regulation of NDRG1 in human brain cancer cells

Time- and oxygen-dependent expression and regulation of NDRG1 in human brain cancer cells

Hypoxia‐like transcriptional activation in TMT‐induced degeneration: microarray expression analysis on PC12 cells

Role of ETS Transcription Factors in the Hypoxia-Inducible Factor-2 Target Gene Selection

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