Pathways affected by asbestos exposure in normal and tumour tissue of lung cancer patients

“…Not only have models of gene profiling been developed in rodents as a means of classifying the toxicity of compounds to liver and other organs (Steiner et al 2004), but this concept has previously been applied to define early molecular events following exposure of normal human bronchial epithelial cells (NHBEs) (Belitskaya-Levy et al 2007), murine nontransformed alveolar type II epithelial (C10) cells (Ramos-Nino et al 2003), human lung adenocarcinoma (A549) cells (Hevel et al 2008; Nymark et al 2007), SV40-transformed bronchial epithelial (Beas-2B) cells, and SV40-immortalized pleural mesothelial (MET5A) cells (Nymark et al 2007) to asbestos. Transcript profiling has also been used to identify differentially regulated pathways in lung and tumor tissues of asbestos-exposed and non-exposed lung cancer patients (Ruosaari et al 2008), as well as to examine gene changes in human pulmonary artery endothelial cells (HPAEC) exposed to ultrafine particles (Karoly et al 2007). A summary of results from several of these in vitro studies using asbestos can be found in Table 3.…”

Section: Discussionmentioning

confidence: 99%

Utilization of Gene Profiling and Proteomics to Determine Mineral Pathogenicity in a Human Mesothelial Cell Line (LP9/TERT-1)

Hillegass

Shukla

MacPherson

et al. 2010

Journal of Toxicology and Environmental Health, Part A

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Background-Identifying and understanding the early molecular events that underscore mineral pathogenicity using in vitro screening tests is imperative, especially given the large number of synthetic and natural fibers and particles being introduced into the environment. The purpose of the work described here was to examine the ability of gene profiling (Affymetrix microarrays) to predict the pathogenicity of various materials in a human mesothelial cell line (LP9/TERT-1) exposed to equal surface area concentrations (15×10 6 or 75×10 6 μm 2 /cm 2 ) of crocidolite asbestos, nonfibrous talc, fine titanium dioxide (TiO 2 ), or glass beads for 8 or 24 h. Since crocidolite asbestos caused the greatest number of alterations in gene expression, multiplex analysis (Bio-Plex) of proteins released from LP9/TERT-1 cells exposed to crocidolite asbestos was also assessed to reveal if this approach might also be explored in future assays comparing various mineral types. To verify that LP9/TERT-1 cells were more sensitive than other cell types to asbestos, human ovarian epithelial cells (IOSE) were also utilized in microarray studies. Upon assessing changes in gene expression via microarrays, principal component analysis (PCA) of these data was used to identify patterns of differential gene expression.

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“…A recent review by Nymark et al, (2008), provides an excellent overview of the many molecular and genetic changes in asbestos-related lung cancer. In a comparison of matched normal and lung tumor tissue, Ruosaari et al, (2008) have identified several functional pathways significantly different between asbestosexposed and nonexposed lung cancer patients including ion transport, NF-jB signaling, DNA repair, and spliceosome and nucleosome complexes. Furthermore, many pathways downregulated in asbestos-exposed subjects were related to protein ubiquination, involved in multiple cell processes, including cell cycling, apoptosis, and DNA repair.…”

Section: Discussionmentioning

confidence: 99%

ADAM28: A potential oncogene involved in asbestos‐related lung adenocarcinomas

Wright

Larsen

Hayward

et al. 2010

Genes Chromosomes & Cancer

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Asbestos-related lung cancer accounts for 4-12% of all lung cancers worldwide. Since putative mechanisms of carcinogenesis differ between asbestos and tobacco induced lung cancers, tumors induced by the two agents may be genetically distinct. To identify gene expression biomarkers associated with asbestos-related lung tumorigenicity we performed gene expression array analysis on tumors of 36 patients with primary lung adenocarcinoma, comparing 12 patients with lung asbestos body counts above levels associated with urban dwelling (ARLC-AC: asbestos-related lung cancer-adenocarcinoma) with 24 patients with no asbestos bodies (NARLC-AC: non-asbestos related lung cancer-adenocarcinoma). Genes differentially expressed between ARLC-AC and NARLC-AC were identified on fold change and P value, and then prioritized using gene ontology. Candidates included ZNRF3, ADAM28, PPP1CA, IRF6, RAB3D, and PRDX1. Expression of these six genes was technically and biologically replicated by qRT-PCR in the training set and biologically validated in three independent test sets. ADAM28, encoding a disintegrin and metalloproteinase domain protein that interacts with integrins, was consistently upregulated in ARLC across all four datasets. Further studies are being designed to investigate the possible role of this gene in asbestos lung tumorigenicity, its potential utility as a marker of asbestos related lung cancer for purposes of causal attribution, and its potential as a treatment target for lung cancers arising in asbestos exposed persons.

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Pathways affected by asbestos exposure in normal and tumour tissue of lung cancer patients

Cited by 15 publications

References 35 publications

Induction of altered mRNA expression profiles caused by fibrous and granular dust

Induction of altered mRNA expression profiles caused by fibrous and granular dust

Utilization of Gene Profiling and Proteomics to Determine Mineral Pathogenicity in a Human Mesothelial Cell Line (LP9/TERT-1)

ADAM28: A potential oncogene involved in asbestos‐related lung adenocarcinomas

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