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

Our plain-English summary of Gene expression profiles in asbestos-exposed epithelial and mesothelial lung cell lines, by P. Nymark, P.M. Lindholm, M.V. Korpela, et al (BMC Genomics, 2007).

The study

• Authors: P. Nymark, P.M. Lindholm, M.V. Korpela, L. Lahti, S. Ruosaari, S. Kaski, J. Hollmén, S. Anttila, V.L. Kinnula, S. Knuutila
• Journal: BMC Genomics
• Published: 2007;8:62
• Cited by: 63 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This was a laboratory study of human lung cells in culture, not of people. The authors exposed three cell lines to crocidolite asbestos: A549 lung adenocarcinoma cells, Beas-2B bronchial epithelial cells and MeT5A pleural mesothelial cells. They then measured which genes changed activity compared with unexposed cells, at time points from 1 hour to 48 hours, plus 7 days for A549. Under the authors' analysis criteria, no gene categories linked to biological processes showed changes common to all three cell lines after 1 hour, but 10 did after 48 hours. Cluster analysis found 12 significant gene groups in A549, 16 in Beas-2B and 3 in MeT5A. Five collagen genes appeared in significant clusters in all cell lines. A comparison of A549 and Beas-2B listed 21 chromosome regions as potential asbestos 'hotspots', the most significant being 2p22. The genes TXNDC and BNIP3L appeared in all analyses. The authors noted that cell experiments cannot precisely reflect conditions in the body, and that many changes probably reflect general responses to toxic substances. The authors concluded that the study identified several targets for further investigation in relation to asbestos-associated diseases.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) gene expression study: human lung cell lines exposed to asbestos in culture and compared with unexposed control cultures over time using Affymetrix microarrays
• Who was studied: Three human cell lines: A549 (lung adenocarcinoma), Beas-2B (SV40-transformed bronchial epithelial) and MeT5A (SV40-immortalized pleural mesothelial). A549 and Beas-2B were sampled at 1h, 6h, 24h and 48h, with an extra 7-day point for A549. MeT5A was sampled at 1h and 48h.
• Exposure: Crocidolite asbestos (International Union Against Cancer standard) added to the culture medium at 2 μg/cm2 for A549 and Beas-2B cells and 1 μg/cm2 for MeT5A cells. The unit is printed in the text as 'βg/cm2', apparently micrograms.
• Main results:
  • In the Gene Ontology analysis, 351 unique branches of biological processes were enriched in at least one cell line at at least one time point.
  • The analysis counted only GO branches with at least three enriched terms. Under these criteria, no commonly enriched processes (gene-expression categories) were found in all three cell lines after 1 h of exposure, and 10 common GO terms were identified after 48 h.
  • The number of processes shared by the cell lines increased with time.
  • The only upregulated process common to all three cell lines at 48h was 'sensory perception of smell'.
  • Cluster analysis found 12 significant clusters in A549, 16 in Beas-2B and 3 in MeT5A.
  • The most significant A549 cluster (cluster 5) was enriched for genes in nine of 18 chromosomal regions previously identified with copy number changes in asbestos-associated lung cancer.
  • 559 previously identified asbestos-associated genes, represented by 1,362 probe sets on the array, were checked against the clusters.
  • Five collagen genes were found in significant clusters in all three cell lines.
  • Canonical correlation analysis of A549 and Beas-2B identified 21 chromosomal regions (p-value less than 0.03; q-value less than 0.38, an expected false discovery rate below 38%).
  • The most significant region in the canonical correlation analysis was 2p22.
  • The top 10 regions from the canonical correlation analysis were significantly associated with germline 8-oxoguanine-rich regions (p = 0.024).
  • The genes TXNDC and BNIP3L were represented in all analyses.
• The authors' conclusion: The authors concluded that the study identifies several targets for further investigation in relation to asbestos-associated diseases.
• Limitations the authors state:
  • Laboratory cell experiments cannot precisely reflect conditions and mechanisms in the body.
  • Interactions with inflammatory cells and with the extracellular matrix are missing in the experiment.
  • Beas-2B and MeT5A are SV40-immortalized cells, which may account for some of the gene expression changes.
  • Many measured changes are probably general cellular responses to foreign toxic substances rather than asbestos-specific effects.
  • The MeT5A cell line was left out of the canonical correlation analysis because it had too few time points.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Crocidolite.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Lung Cancer, Crocidolite.

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