Gene expression profiles in asbestos-exposed epithelial and mesothelial lung cell lines.
BACKGROUND
Asbestos has been shown to cause chromosomal damage and DNA aberrations. Exposure to asbestos causes many lung diseases e.g. asbestosis, malignant mesothelioma, and lung cancer, but the disease-related processes are still largely unknown. We exposed the human cell lines A549, Beas-2B and Met5A to crocidolite asbestos and determined time-dependent gene expression profiles by using Affymetrix arrays. The hybridization data was analyzed by using an algorithm specifically designed for clustering of short time series expression data. A canonical correlation analysis was applied to identify correlations between the cell lines, and a Gene Ontology analysis method for the identification of enriched, differentially expressed biological processes.


RESULTS
We recognized a large number of previously known as well as new potential asbestos-associated genes and biological processes, and identified chromosomal regions enriched with genes potentially contributing to common responses to asbestos in these cell lines. These include genes such as the thioredoxin domain containing gene (TXNDC) and the potential tumor suppressor, BCL2/adenovirus E1B 19kD-interacting protein gene (BNIP3L), GO-terms such as "positive regulation of I-kappaB kinase/NF-kappaB cascade" and "positive regulation of transcription, DNA-dependent", and chromosomal regions such as 2p22, 9p13, and 14q21. We present the complete data sets as Additional files.


CONCLUSIONS
This study identifies several interesting targets for further investigation in relation to asbestos-associated diseases.
Nymark
Penny
P
Health and Work Ability, Biological Mechanisms and Prevention of Work-related Diseases, Finnish Institute of Occupational Health, Helsinki, Finland. penny.nymark@helsinki.fi
Lindholm
Pamela M
PM
Korpela
Mikko V
MV
Lahti
Leo
L
Ruosaari
Salla
S
Kaski
Samuel
S
Hollmén
Jaakko
J
Anttila
Sisko
S
Kinnula
Vuokko L
VL
Knuutila
Sakari
S
D017638:Asbestos, Crocidolite / Q000633:toxicity*; D002460:Cell Line; D016000:Cluster Analysis; D004848:Epithelium / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008171:Lung Diseases / Q000139:chemically induced; D009693:Nucleic Acid Hybridization
D017638:Asbestos, Crocidolite