Human Gene Set: CHENG_RESPONSE_TO_NICKEL_ACETATE


Standard name CHENG_RESPONSE_TO_NICKEL_ACETATE
Systematic name M19667
Brief description Genes down-regulated in HPL1D cells (lung epithelium) upon exposure to nickel acetate [PubChem=9756].
Full description or abstract Occupational exposure to nickel compounds is associated with lung cancer risk; both genotoxic and epigenetic mechanisms have been proposed. For comprehensive examination of the acute effects of nickel(II) acetate on gene expression in cultured human peripheral lung epithelial HPL1D cells, microarray analyses were carried out with cDNA chips (approximately 8000 cDNAs). Cells were exposed for 24 h to nontoxic (50, 100, and 200 microM) or toxic (400, 800, and 1600 microM) nickel(II) concentrations. Cluster analysis was applied to the 868 genes with > or = 2-fold change at any concentration. Two main clusters showed marked up- or down-regulation at the highest, toxic concentrations. The data further subdivided into 10 highly cohesive clusters with high probability, and of these only 2 had the same response trend at low nontoxic as at high concentrations, an observation of clear relevance to the process of high- to low-dose extrapolation in risk assessment. There were 113 genes showing > or = 2-fold change at the three lower nontoxic concentrations, those most relevant to in vivo carcinogenesis. In addition to expected responses of metallothionein, ferritin, and heat-shock proteins, the results revealed for the first time changed expression of some potential cancer-related genes in response to low-dose Ni(II): RhoA, dyskerin, interferon regulatory factor 1, RAD21 homologue, and tumor protein, translationally controlled. Overall, most of the genes impacted by nontoxic concentrations of nickel(II) acetate related to gene transcription, protein synthesis and stability, cytoskeleton, signaling, metabolism, cell membrane, and extracellular matrix.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 12915101   Authors: Cheng RY,Zhao A,Alvord WG,Powell DA,Bare RM,Masuda A,Takahashi T,Anderson LM,Kasprzak KS
Exact source Table 2
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Source species Homo sapiens
Contributed by John Newman (University of Washington)
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identifier namespace		 Human_NCBI_Gene_ID
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Version history 3.0: Renamed from NI2_LUNG_DN

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