SV40 and cell cycle perturbations in malignant mesothelioma

Our plain-English summary of SV40 and cell cycle perturbations in malignant mesothelioma, by J.R. Testa, A. Giordano (Seminars in Cancer Biology, 2001).

The study

• Authors: J.R. Testa, A. Giordano
• Journal: Seminars in Cancer Biology
• Published: 2001;11(1):31-8
• Type of article: Review
• Cited by: 42 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Although epidemiological findings have established that exposure to asbestos fibers is the major cause of malignant mesothelioma (MM), recent studies have implicated simian virus 40 (SV40) in the etiology of some of these tumors. Cytogenetic and molecular genetic evidence suggests that multiple somatic genetic events are required for tumorigenic conversion of a mesothelial cell. As with many other types of cancer, in MM critical oncogenic events exert their action via perturbations of the cell cycle. Interactions between the retinoblastoma (Rb) family of proteins and oncoproteins encoded by SV40 lead to cell cycle alterations. Likewise, inhibition of the p53 tumor suppressor by SV40 can inactivate a crucial cell cycle checkpoint, thereby permitting cells to undergo mitosis regardless of the presence of DNA damage. Many MMs exhibit loss and/or inactivation of the tumor suppressors p16(INK4a)and p14(ARF), components of the pRb and p53 cell cycle regulatory pathways, respectively. Recent investigations have demonstrated that SV40 large T antigen, isolated from frozen biopsies of human MM specimens, binds to and inactivates various tumor suppressor gene products such as pRb and p53. In this review, we discuss how SV40-oncosuppressor interactions can lead to functional alterations of the pRb- and p53-dependent cell cycle regulatory pathways and thereby contribute to neoplastic transformation of human mesothelial cells.

Copyright 2001 Academic Press.

In plain English

This article is a review, not a new study. The authors discussed published laboratory research on how simian virus 40 (SV40) might contribute to malignant mesothelioma. They described asbestos as a major cause of the disease. They focused on how a viral protein, SV40 large T antigen, binds and disables the tumor-suppressor proteins pRb and p53, which normally help control cell division. One cited study found SV40-like DNA in 29 of 48 (60%) human mesotheliomas. Two other groups did not find such sequences, and Finnish specimens consistently tested negative. Another cited study found SV40-like sequences in 30 of 35 (86%) mesotheliomas. The review also described frequent loss of the p16INK4a gene: one cited study reported deletions in 34 of 40 (85%) mesothelioma cell lines and five of 23 (22%) tumor samples. In a cited rat cell experiment, SV40-infected cells exposed to asbestos did not show the slowed growth seen in rat mesothelial cells treated with asbestos alone. The authors concluded that asbestos and the SV40 protein might act as co-carcinogens.

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: review of published laboratory, tissue and animal research
• Who was studied: No study population of its own; the review discussed published analyses of human mesothelioma specimens and cell lines, hamster experiments and rat mesothelial cell experiments
• Exposure: Simian virus 40 (SV40) and its large T antigen, considered together with asbestos fibers (no fiber type specified)
• Main results:
  • A cited study (Carbone et al.) found SV40-like DNA in 29 of 48 (60%) human mesotheliomas
  • Two groups of investigators did not find such DNA sequences in their mesothelioma specimens, and Finnish mesothelioma specimens consistently tested negative for SV40
  • A cited study (De Luca et al.) found SV40-like sequences in 30 of 35 (86%) mesotheliomas
  • Mutations of the p53 gene (TP53) are rarely seen in mesothelioma; one cited study found TP53 abnormalities in three of 17 mesothelioma cell lines
  • A cited study found homozygous deletions of the p16INK4a gene in 34 of 40 (85%) mesothelioma cell lines and five of 23 (22%) tumor samples
  • In a cited experiment, rat mesothelial cells treated with asbestos grew more slowly, but SV40-infected cells exposed to asbestos did not
  • In a cited animal study, pericardial and pleural mesotheliomas developed in 100% of Syrian hamsters injected in the pleural space with wild-type SV40
• The authors' conclusion: The authors concluded that asbestos and SV40 large T antigen might act as co-carcinogens, letting mesothelial cells divide unchecked and build up further genetic changes
• Limitations the authors state:
  • The authors noted that the much higher rate of p16INK4a changes in cell lines than in primary tumors may reflect a laboratory culturing effect

Topics

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

Medical terms in this study, explained in our Lexicon: SV40, Malignant Mesothelioma, Etiology, Mesothelial Cells, Tumor Suppressor Gene.

Related studies

• Alterations of the p16(INK4) locus in human malignant mesothelial tumors — T. Hirao, R. Bueno, et al. (2002)
• Analysis of cell cycle disruptions in cultures of rat pleural mesothelial cells exposed to asbestos fibers — V. Levresse, A. Renier, et al. (1997)
• Effect of simian virus large T antigen expression on cell cycle control and apoptosis in rat pleural mesothelial cells exposed to DNA damaging agents — V. Levresse, S. Moritz, et al. (1998)
• Asbestos exposure predicts cell cycle control gene promoter methylation in pleural mesothelioma — B.C. Christensen, J.J. Godleski, et al. (2008)
• Aberrant expression of cell cycle regulatory genes predicts overall and disease free survival in malignant pleural mesothelioma patients — A.A. Bahnassy, A.R. Zekri, et al. (2012)
• Effects of 6-month daily supplementation with oral beta-carotene in combination or not with benzo[a]pyrene on cell-cycle markers in the lung of ferrets — A. Fuster, C. Picó, et al. (2008)

Browse more research in Seminars in Cancer Biology, or return to medical research.