Asbestos and the mesothelial cell: a molecular trail to mitogenic stimuli and suppressor gene suspects

Our plain-English summary of Asbestos and the mesothelial cell: a molecular trail to mitogenic stimuli and suppressor gene suspects, by B.I. Gerwin (American Journal of Respiratory Cell and Molecular Biology, 1994).

The study

• Author: B.I. Gerwin
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 1994;11(5):507-8
• Type of article: Review
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

This perspective article reviewed evidence on the molecular events that might link asbestos exposure to mesothelioma. The author noted that, although the association between asbestos exposure and mesothelioma was well documented, no clear set of molecular changes had been identified. The article summarised studies showing that asbestos fibres activated macrophages and recruited inflammatory cells, that asbestos-exposed mesothelial cells produced interleukin-8, that inflammatory cytokines such as TNF-α were likely to account for fibre-induced mesothelial cell proliferation and collagen synthesis, that asbestos induced c-fos and c-jun, and that fibres caused mitotic damage. It then reviewed tumour suppressor genes. Mutation or loss of expression of p53 had been found in 3 of 20 human mesothelioma cell lines. Rb protein expression in the lines was equivalent to that in normal mesothelial cells, although one antibody study suggested a possible Rb mutation. Nineteen of 20 cell lines had lost p16 protein expression through homozygous deletion, and the chromosome 9 region containing this gene was frequently deleted in mesothelioma. The author highlighted the Wilms tumour gene WT1, which is expressed in normal adult mesothelium. In one study, 32 asbestos-linked mesotheliomas showed no WT1 mutations in exon 6, while one multicystic tumour carried a mutation. The author concluded that analyses of WT1 interactions in mesothelioma might provide exciting data on the pathogenesis of the disease.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This short Perspective article, by an author at the National Cancer Institute, did not report a new study. It reviewed published laboratory research, plus some unpublished findings shared by colleagues, on how asbestos may affect mesothelial cells (the cells lining the chest and abdominal cavities) and which genes may be involved in mesothelioma. The author described studies showing that asbestos exposure can set off inflammation and growth signals in these cells. On tumor suppressor genes, the author cited a study that found mutation or loss of p53 in three of 20 human mesothelioma cell lines, and reported that 19 of 20 mesothelioma cell lines had lost the p16 protein through deletion. A cited study of 33 mesothelioma specimens found no mutations in one region of the Wilms tumor gene WT1 in the 32 cases linked to asbestos exposure. One multicystic tumor did carry a mutation. The author noted that the relevance of the cell-line findings to actual tumor tissue remained to be established. The author suggested that studying how WT1 interacts with other proteins in mesothelioma may provide data on how the disease develops.

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: Perspective (short commentary reviewing published and some unpublished laboratory research); no original study
• Who was studied: No study population of its own; the article discusses published laboratory studies of mesothelial cells, human mesothelioma cell lines and mesothelioma specimens
• Exposure: Asbestos fibers in general (no fiber type named), in the context of laboratory and animal studies of inhalation or intraperitoneal injection
• Main results:
  • A cited study (reference 13) found mutation or loss of expression of p53 in three of 20 human mesothelioma cell lines
  • Re-examination of the same cell lines (unpublished, personal communication) found no correlation between high MDM2 expression and wild-type p53
  • The same unpublished work found retinoblastoma (Rb) protein expression in all the lines equivalent to normal human mesothelial cells, confirming an earlier study (reference 14)
  • Analysis of mesothelioma cell lines (reference 17 and personal communication) indicated that 19 of 20 had lost expression of the p16 protein through homozygous deletion
  • A cited study (reference 22) of 33 mesothelioma specimens found no WT1 mutations in exon 6 in the 32 cases linked to asbestos exposure
  • In that cited study, one multicystic tumor contained a somatic WT1 mutation at codon 273
  • The author noted that four cases of malignant mesothelioma had been reported in young adults cured of Wilms tumor (reference 29)
• The authors' conclusion: The author stated that no suppressor gene had been clearly linked to mesothelioma. The author suggested that studying WT1 interactions in mesothelioma may provide data on how the disease develops.
• Limitations the authors state:
  • The author stated that the relevance of the cell-line observations to primary tumor material remained to be established
  • The author stated that the relative abundance of differently spliced WT1 species and the protein complexes they form remained to be examined

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Asbestos Exposure, Mesothelioma, Macrophage, Cytokine, Collagen, Homozygous Deletion, Mesothelium.

Related studies

• Tumor suppressor alterations cooperate to drive aggressive mesotheliomas with enriched cancer stem cells via a p53-miR-34a-c-Met axis — C.W. Menges, Y. Kadariya, et al. (2014)
• Spontaneously immortalized mouse mesothelial cells display characteristics of malignant transformation — A.L. Sherwood, S.E. Mutsaers, et al. (2008)
• Oncogenes and tumor-suppressor genes in mesothelioma--a synopsis — J.F. Lechner, J. Tesfaigzi, et al. (1997)
• TAZ activation by Hippo pathway dysregulation induces cytokine gene expression and promotes mesothelial cell transformation — A. Matsushita, T. Sato, et al. (2019)
• Progressive aberrant methylation of the RASSF1A gene in simian virus 40 infected human mesothelial cells — S. Toyooka, M. Carbone, et al. (2002)
• Human mesothelial cells are unusually susceptible to simian virus 40-mediated transformation and asbestos cocarcinogenicity — M. Bocchetta, I. Di Resta, et al. (2000)

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