The retinoblastoma gene family pRb/p105, p107, pRb2/p130 and simian virus-40 large T-antigen in human mesotheliomas

Our plain-English summary of The retinoblastoma gene family pRb/p105, p107, pRb2/p130 and simian virus-40 large T-antigen in human mesotheliomas, by A. De Luca, A. Baldi, V. Esposito, et al (Nature Medicine, 1997).

The study

• Authors: A. De Luca, A. Baldi, V. Esposito, C.M. Howard, L. Bagella, P. Rizzo, M. Caputi, H.I. Pass, G.G. Giordano, F. Baldi, M. Carbone, A. Giordano
• Journal: Nature Medicine
• Published: 1997;3(8):913-6
• Cited by: 179 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The oncoprotein of simian virus-40, SV40 large T-antigen (Tag), is reported to target and to inactivate growth suppressive proteins such as the retinoblastoma family and p53 (ref. 4, 5), leading to transformation of human cell lines in vitro, tumor production in rodents, and detection of Tag in several human cancers including mesotheliomas. The retinoblastoma family contains three members, pRb, p107 and pRb2/p130 (ref. 9), that are phosphorylated in a cell cycle-dependent manner, have cell growth suppressive properties and bind to specific members of the E2F family and various cyclins. Even though mesotheliomas are among the most aggressive human cancers, alterations of important cell-cycle "controllers," such as the Rb family genes, have never been reported in these tumors. We found the presence of SV40-like sequences in 86% of 35 archival specimens of mesothelioma. We also demonstrated that SV40 Tag, isolated from frozen biopsies of human mesothelioma, binds each of the retinoblastoma family proteins, pRb, p107 and pRb2/p130, in four of four specimens. We propose that the tumorigenic potential of SV40 Tag in some human mesotheliomas may arise from its ability to interact with and thereby inactivate several tumor and/or growth suppressive proteins.

In plain English

This laboratory study examined mesothelioma tumor tissue for signs of simian virus 40 (SV40), a monkey virus, and for three related growth-control proteins (pRb, p107 and pRb2/p130). The authors studied 35 archival specimens (17 epithelial, 6 sarcomatoid and 12 mixed mesotheliomas), obtained by open biopsies or pleurectomies, from the Second University of Naples, Italy. They also studied four frozen specimens from the U.S. National Cancer Institute. SV40-like DNA was detected in 30 of the 35 samples (86%). The SV40 large T-antigen protein was detected in all four frozen specimens. In test-tube experiments, the T-antigen in extracts from these four specimens bound laboratory-made versions of each of the three growth-control proteins. Levels of these proteins did not differ statistically between tumor types and did not correlate statistically with overall patient survival. The authors could not demonstrate asbestos exposure in the majority of patients. They noted that too few samples lacked the viral protein to compare outcomes statistically. The authors concluded that SV40 could play a role in the development of mesothelioma by impairing the function of tumor-suppressing proteins.

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 mesothelioma tumor specimens, using immunohistochemistry, PCR for viral DNA, RT-PCR, and test-tube protein-binding experiments
• Who was studied: 35 archival mesothelioma specimens (17 epithelial, 6 sarcomatoid, 12 mixed) from open biopsies or pleurectomies, held at the Institute of Surgical Pathology, Second University of Naples, Italy, from patients aged 34 to 80 years. Also four frozen mesothelioma specimens from the Thoracic Oncology Section, National Cancer Institute, Bethesda, Maryland. Dates are not given.
• Exposure: Presence of SV40 large T-antigen DNA, RNA and protein in the tumors. No asbestos fiber measurements were reported. The authors state they could not demonstrate asbestos exposure in the majority of patients.
• Main results:
  • The SV40 Tag DNA fragment (105 base pairs) was detected in 30 of the 35 archival mesothelioma samples (86%).
  • Direct sequencing of four of the amplified fragments confirmed that they matched the Rb-binding region of SV40 Tag.
  • A 90 kDa protein band (SV40 Tag) was detected in all four frozen mesothelioma samples and in SV40-transformed COS-7 cells. It was not detected in the HL60 control cell line.
  • In a test-tube experiment, protein extracts from the four frozen mesothelioma samples were incubated with laboratory-made (in vitro translated) pRb, p107 and pRb2/p130. The authors report that SV40 Tag from the biopsies bound each of these proteins in four of four specimens.
  • Among the 35 archival specimens, medium to high pRb expression was seen in all but one specimen.
  • Expression of the three proteins did not differ statistically between epithelial, sarcomatoid and mixed mesotheliomas.
  • Expression of the three proteins did not correlate statistically with overall patient survival.
• The authors' conclusion: The authors concluded that their results, together with an accompanying paper, support the conclusion that SV40 could play a role in the development of mesothelioma by impairing the function of several tumor suppressor and/or growth suppressive proteins.
• Limitations the authors state:
  • Outcomes for tumors with and without SV40 Tag could not be compared statistically, because only a small number of samples lacked Tag.
  • The tissue extracts contained other material besides tumor cells, such as vascular cells and connective tissue, which created technical difficulties for the protein experiments.

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.

Related studies

• Simian virus-40 large-T antigen binds p53 in human mesotheliomas — M. Carbone, P. Rizzo, et al. (1997)
• Human mesotheliomas contain the simian virus-40 regulatory region and large tumor antigen DNA sequences — H.I. Pass, J.S. Donington, et al. (1998)
• Human T cell responses to endogenously presented HLA-A*0201 restricted peptides of Simian virus 40 large T antigen — M.P. Velders, M.F. Macedo, et al. (2001)
• Simian virus 40 large T antigen (SV40LTAg) primer specific DNA amplification in human pleural mesothelioma tissue — C. Pepper, B. Jasani, et al. (1996)
• Does Simian Virus 40 (SV40) Have a Role in UK Malignant Pleural Mesothelioma? No Role is Identified in a Sensitive RNA In Situ Hybridization Study on Potentially Affected Birth Cohorts — F.S. Alchami, R.L. Attanoos, et al. (2020)
• 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)

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