Simian virus-40 large-T antigen binds p53 in human mesotheliomas

Our plain-English summary of Simian virus-40 large-T antigen binds p53 in human mesotheliomas, by M. Carbone, P. Rizzo, P.M. Grimley, et al (Nature Medicine, 1997).

The study

• Authors: M. Carbone, P. Rizzo, P.M. Grimley, A. Procopio, D.J. Mew, V. Shridhar, A. de Bartolomeis, V. Esposito, M.T. Giuliano, S.M. Steinberg, A.S. Levine, A. Giordano, H.I. Pass
• Journal: Nature Medicine
• Published: 1997;3(8):908-12
• Cited by: 221 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

We found that simian virus 40 (SV40) induces mesotheliomas in hamsters and that 60% of human mesotheliomas contain and express SV40 sequences, results now confirmed by others [ref. 3-5, and presentations by D. Griffiths & R. Weiss, F. Galateau-SallE, and H.I.P. at "Simian virus 40: A possible human polyoma virus," NIH workshop, 27-28 January 1997, Bethesda, MD (transcript available through SAG Corp., Washington, DC 20008)]. Mesothelioma, an aggressive malignancy resistant to therapy, originates from the serosal lining of the pleural, pericardial and peritoneal cavities. The incidence of mesothelioma continues to increase worldwide because of exposure to crocidolite asbestos. However, at least 20% of mesotheliomas in the United States are not associated with asbestos exposure, and only a minority of people exposed to high concentrations of asbestos develop mesothelioma. Thus, other carcinogens may induce mesothelioma in individuals not exposed to asbestos, and/or may render particular individuals more susceptible to the carcinogenic effect of asbestos. We investigated whether the expression of the SV40 large T-antigen (Tag) interferes with the normal expression of the tumor suppressor gene p53 in human mesotheliomas. We found that SV40 Tag retains its ability to bind and to inactivate p53, a cellular protein that when normally expressed plays an important role in suppressing tumor growth and in inducing sensitivity to therapy. Our findings do not establish a cause-and-effect relation, but indicate that the possibility that SV40 contributes to the development of human mesotheliomas should be carefully investigated.

In plain English

This laboratory study examined 51 mesotheliomas and one fibrous tumor of the pleura (also called benign mesothelioma). The samples came from patients on surgical protocols at the US National Cancer Institute. The authors tested whether large T antigen (Tag), a protein made by simian virus 40 (SV40), binds and disables p53, a protein that normally helps suppress tumors. The paper does not report asbestos-exposure data for these patients. In the mesotheliomas, Tag staining was significantly associated with p53 staining (P = 0.0082 scoring staining strength; P = 0.0046 scoring the share of stained cells). The fibrous tumor was negative for both. Gene testing found p53 mutations in only 3 of 29 specimens evaluated. p21, a protein that working p53 normally switches on, was detected in only 1 of 52 samples. In cells grown from mesotheliomas, Tag and p53 were pulled down together, suggesting a physical link. The authors concluded that their results suggest that, in mesotheliomas containing SV40-like sequences, a Tag-like protein binds, stabilizes and inactivates normal p53. They stated that their findings do not establish cause and effect.

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 study of human tumor specimens (immunostaining, in situ hybridization, p53 mutation analysis, and protein co-precipitation experiments)
• Who was studied: Tumor samples (51 mesotheliomas and 1 fibrous tumor of the pleura) from patients on surgical protocols at the National Cancer Institute (USA). Dates of collection were not given.
• Exposure: Expression of SV40 large T antigen (Tag) in the tumors and whether it binds and inactivates p53. The paper does not report asbestos-exposure data for the patients in this study.
• Main results:
  • In the mesotheliomas, Tag expression was significantly associated with p53 coexpression when staining strength was used (two-sided test, P = 0.0082).
  • The association was also significant when the grade (percentage of positive cells) was used (two-sided test, P = 0.0046).
  • The single fibrous tumor of the pleura was negative for both Tag and p53.
  • Of 34 mesothelioma samples studied by in situ hybridization, 14 were positive for both Tag and p53 mRNA and 8 were negative for both. The remaining 12 could not be evaluated because of high background.
  • p53 mutations were found in only 3 of 29 specimens evaluated by SSCP and RFLP studies. Full sequencing of two mesotheliomas found no p53 mutations.
  • In cells cultured from two human mesothelioma samples, co-precipitation produced a 90 kDa band (Tag) and a 53 kDa band (p53). The authors took this as suggesting a physical association between Tag and p53.
  • p21 was detectable in only one of the 52 samples. The authors interpreted this as suggesting that p53 was biologically inactive.
• The authors' conclusion: The authors concluded that their results suggest that, in mesotheliomas containing SV40-like sequences, a protein indistinguishable from Tag (Tag-like) binds, stabilizes and inactivates wild-type p53.
• Limitations the authors state:
  • The authors stated that their findings do not establish a cause-and-effect relation between SV40 and mesothelioma.
  • The mutation screening method used (PCR combined with SSCP) does not detect all possible point mutations.
  • Matched normal tissue for comparison was available for only 25 of the mesotheliomas.
  • In experiments on the frozen tumor specimens, p53 could not be clearly identified in the co-precipitation because of high background staining.
  • 12 of the 34 samples studied by in situ hybridization could not be evaluated.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, SV40, Pericardial, Crocidolite, Asbestos Exposure, Carcinogenic, Tumor Suppressor Gene.

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