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

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.

Figure 1

Overall study design.

Figure 2

Profiles of the most significant clusters in A549 (A-C), Beas-2B (D-F) and MeT5A (G-I) cells. The X-axis shows the time points from 0 h-48 h (or in the case of A549, 7 days) and the Y-axis the expression ratio profile that is representative of all probe sets in the cluster. Due to the correlation-based distance measure used in the clustering method [48], the scale of the Y-axis is not relevant.

Figure 3

The significance of each cluster in A549 (A), Beas-2B (B), and MeT5A (C). The X-axis shows the number of expected probe sets and the Y-axis the number of assigned probe sets in each cluster. The clusters above the line are considered statistically significant based on permutation tests.