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SOFT file
| Title / Description |
Whole genome expression profile of lung epithelial cells following chronic arsenic exposure |
| Accession |
GSE33520
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| Summary |
This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide in vitro to elucidate cancer promoting gene signaling networks (GSNs) associated with As-transformed (B-As) cells. Following a six month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. As exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased ROS protection suggesting mitochondrial dysfunction. Carcinogenic initiation via ROS and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ GSN identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome GSN profile provide an in vitro As model for future lung cancer signaling research and data for chronic As exposure risk assessment. |
| Organism |
Homo sapiens |
| Platform |
GPL6480 |
| Normalized |
False |
| Parsed SOFT file |
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Metadata
| Differential expression method |
Characteristic Direction
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| Cutoff |
500 |
| Cell_type |
Lung epithelial cells (BEAS-2B) |
| Drug_id |
CID 518740 |
| Drug_name |
Arsenic trioxide - 2.5uM - 6 months |
| Organism |
Human |
Visualizations
| Principal Component Analysis |
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| Hierarchical clustering |
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External Links and Downloads
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Gene lists
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Enrichr
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L1000CDS2
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PAEA
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