Gene expression profiles in asbestos-exposed epithelial and mesothelial lung cell lines

Penny Nymark^*¹^,2 , Pamela M Lindholm^*² , Mikko V Korpela³ , Leo Lahti³ , Salla Ruosaari¹^,2^,3 , Samuel Kaski³ , Jaakko Hollmén³ , Sisko Anttila¹ , Vuokko L Kinnula⁴ and Sakari Knuutila²

¹Health and Work Ability, Biological Mechanisms and Prevention of Work-related Diseases, Finnish Institute of Occupational Health, Helsinki, Finland

²Department of Pathology, Haartman Institute and HUSLAB, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland

³Helsinki Institute for Information Technology, Laboratory of Computer and Information Science, Helsinki University of Technology, Espoo, Finland

⁴Department of Medicine, Pulmonary Division, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

author email corresponding author email* Contributed equally

BMC Genomics 2007, 8:62doi:10.1186/1471-2164-8-62


Published:	1 March 2007

Abstract

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.

Conclusion

This study identifies several interesting targets for further investigation in relation to asbestos-associated diseases.