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| Status |
Public on Sep 26, 2012 |
| Title |
Whole genome expression profile of lung epithelial cells following chronic arsenic exposure |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| 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.
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| Overall design |
Whole genome expression profiling was conducted on arsenic (III) oxide-exposed human immortalized lung epithelial cells (BEAS-2B) following 6 month in vitro chronic exposure. As2O3 exposed cells (B-As) gene expression were compared to unexposed, passage control (B-Control) cell gene expression. Three B-As and four B-Control biological replicate cDNA samples were analyzed. One technical replicate was performed per biological sample.
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| Contributor(s) |
Stueckle TA, Rojanasakul Y |
| Citation(s) |
22521957 |
| |
| Submission date |
Nov 07, 2011 |
| Last update date |
Jan 23, 2019 |
| Contact name |
Todd A Stueckle |
| E-mail(s) |
tstueckle@cdc.gov
|
| Phone |
304 285-6098
|
| Organization name |
National Institute for Occupational Safety and Health
|
| Department |
Health Effects Laboratory Division
|
| Lab |
Pathology and Physiology Research Branch
|
| Street address |
1095 Willowdale Road
|
| City |
Morgantown |
| State/province |
WV |
| ZIP/Postal code |
26505 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL6480 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version) |
|
| Samples (7)
|
| GSM829378 |
BEAS2B_2.5 μM arsenic trioxide_6month_rep1 |
| GSM829379 |
BEAS2B_2.5 μM arsenic trioxide_6month_rep2 |
| GSM829380 |
BEAS2B_2.5 μM arsenic trioxide_6month_rep3 |
| GSM829381 |
BEAS2B_unexposed passaged_6month_rep1 |
| GSM829382 |
BEAS2B_unexposed passaged_6month_rep2 |
| GSM829383 |
BEAS2B_unexposed passaged_6month_rep3 |
| GSM829384 |
BEAS2B_unexposed passaged_6month_rep4 |
|
| Relations |
| BioProject |
PRJNA148801 |
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