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

Nature Medicine volume 3, pages 913–916 (1997)Cite this article

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 family1–3 and p53 (ref. 4, 5), leading to transformation of human cell lines in vitro, tumor production in rodents6, and detection of Tag in several human cancers including mesotheliomas7,8. The retinoblastoma family contains three members, pRb, p107 and pRb2/p130 (ref. 9), that are phosphorylated in a cell cycle-dependent manner10,11, have cell growth suppressive properties12 and bind to specific members of the E2F family and various cyclins13. 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.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 12 print issues and online access

$259.00 per year

only $21.58 per issue

Buy this article

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

References

  1. DeCaprio, J.A. et al. SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell 54, 275–83 (1988).
    Article CAS Google Scholar
  2. Ludlow, J.W. et al. SV40 large T antigen bind preferentially to an underphosphorylated member of the retinoblastoma susceptibility gene product family. Cell 56, 57–65 (1989).
    Article CAS Google Scholar
  3. Stubdal, H., Zalvide, J. & DeCaprio, J.A. Simian virus 40 large T antigen alters the phosphorylation state of the RB-related proteins p130 and p107. J. Virol. 70, 2781–88 (1996).
    CAS PubMed PubMed Central Google Scholar
  4. Simmons, D.T. Transformation by polymaviruses: Role of tumor suppressor proteins. in: DNA Tumor Viruses: Oncogenic Mechanisms. (eds. Barbanti Brodano, G., Bendinelli, M. & Friedman, H.) 27–50 (Plenum, New York and London, 1995).
    Chapter Google Scholar
  5. Sang, N., Baldi, A. & Giordano, A. The role of tumor suppressors pRb and p53 in cell proliferation and cancer. Mol. Cell. Differ. 3, 1–29 (1995).
    CAS Google Scholar
  6. Carbone, M., Rizzo, P. & Pass, H.I. Simian Virus 40, poliovaccines, and human tumor: a review of recent developments. Ocogene (in the press).
  7. Carbone, M. et al. Simian virus 40-like DNA sequences in human pleural mesothe-lioma. Oncogene 9, 1781–90 (1994).
    CAS Google Scholar
  8. Bergsagel, D.J., Finegold, M.J., Butel, J.S., Kupsky, W.J. & Garcea, R.L. DNA sequences similar to those of simian virus 40 in ependymomas and choroid plexus tumors of childhood. N. Engl. J. Med. 326, 988–93 (1992).
    Article CAS Google Scholar
  9. Paggi, M.G., Baldi, A., Bonetto, F. & Giordano, A. The retinoblastoma protein family in cell cycle and cancer. J. Cell. Biochem. 62, 418–430 (1996).
    Article CAS Google Scholar
  10. Giordano, A., McCall, C., Whyte, P. & Franza, B.R. Human cyclin A and the retinoblastoma protein interact with similar but distinguishable sequences in the adenovirus E1 A gene product. Oncogene 6, 481–485 (1991).
    CAS PubMed Google Scholar
  11. Giordano, A. et al. Cell-cycle regulation of histone HI kinase activity associated with the adenoviral protein E1A. Science 253, 1271–1275 (1991).
    Article CAS Google Scholar
  12. Claudio, P.P. et al. p130/pRb2 has growth suppressive properties similar to yet distinctive from those of retinoblastoma family members pRb and p107. Cancer Res. 54, 5556–5560 (1994).
    CAS Google Scholar
  13. Claudio, P.P. et al. Functional analysis of pRb2/p130 interaction with cyclins. Cancer Res. 56, 2003–2008 (1996).
    CAS PubMed Google Scholar
  14. Fattaey, A.R., Harlow, E. & Helin, K. Independent regions of adenovirus E1 A are required for binding to and dissociation of E2F-protein complexes. Mol. Cell. Biol. 13, 7267–7277 (1993).
    Article CAS Google Scholar
  15. Vousden, K.H. Regulation of the cell cycle by viral oncoproteins. Semin. Cancer Biol. 6, 109–16 (1995).
    Article CAS Google Scholar
  16. Carbone, M. et al. Simian virus-40 large-T antigen binds p53 in human mesotheliomas. Nature Med. 3, XXX–YYY (1997).
    Article Google Scholar
  17. Bartek, J., Vojtesek, B., Grand, R.J., Gallimore, P.H. & Lane, D.P. Cellular localization and T antigen binding of the retinoblastoma protein. Oncogene 7, 101–108 (1992).
    CAS Google Scholar
  18. Lewis, A.M., Jr. Experience with SV40 and adenovirus-SV40 hybrids. in: Biohazards in Biological Research. (eds. Hellman, A., Osman, M. & Pollack, R.) 96–113 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1976).
    Google Scholar
  19. Shah, K. & Nathanson, N. Human exposure to SV40: Review and comment. Am. J. Epidemiol. 103, 1–12 (1976).
    Article CAS Google Scholar
  20. Baldi, A. et al. The Rb2/p130 gene product is a nuclear protein whose phosphorylation is cell cycle regulated. J. Cell. Biochem., 59, 402–408
  21. Baldi, A. et al. Differential expression of Rb2/p130 and p107 in normal human tissues and in primary lung cancer. Clin. Cancer Res. (in the press).
  22. Baldi, A. et al. Differential expression of the retinoblastoma gene family members, pRb/p105, p107, pRb2/p130, in lung cancer. Clin. Cancer Res. 2, 1239–1245 (1996).
    CAS PubMed Google Scholar

Download references

Author information

Author notes

  1. Antonio Giordano: Correspondence should be addressed to A.G.
  2. Antonio De Luca, Alfonso Baldi and Vincenzo Esposito: The first three authors contributed equally to this work

Authors and Affiliations

  1. Department of Pathology, Anatomy & Cell Biology and Sbarro Institute for Cancer Research and Molecular Medicine, Jefferson Medical College, 1020 Locust Street, Philadelphia, Pennsylvania, 19107, USA
    Antonio De Luca, Alfonso Baldi, Vincenzo Esposito, Candace M. Howard, Luigi Bagella & Antonio Giordano
  2. Istituto di Tisiologia e Malattie Respiratorie “S. Marcatili,” Facoltà di Medicina, II Università di Napoli, Via L. Bianchi, Napoli, 80122, Italy
    Vincenzo Esposito & Mario Caputi
  3. Cardinal Bemardin Cancer Center, Cancer Immunology Program, Department of Pathology, Loyola University, 2160 South First Avenue, Chicago, Maywood, Illinois, 60153, USA
    Paoloa Rizzo & Michele Carbone
  4. Karmanos Cancer Institute, Wayne State University, 3990 John Road, Detroit, Michigan, 48201, USA
    Harvey I. Pass
  5. Istituto di Anatomia Patologica, Facoltà di Medicina, II Università di Napoli, Via L. Armanni, Napoli, 80122, Italy
    Giovan Giacomo Giordano & Feliciano Baldi

Authors

  1. Antonio De Luca
  2. Alfonso Baldi
  3. Vincenzo Esposito
  4. Candace M. Howard
  5. Luigi Bagella
  6. Paoloa Rizzo
  7. Mario Caputi
  8. Harvey I. Pass
  9. Giovan Giacomo Giordano
  10. Feliciano Baldi
  11. Michele Carbone
  12. Antonio Giordano

Rights and permissions

About this article

Cite this article

De Luca, A., Baldi, A., Esposito, V. et al. The retinoblastoma gene family pRb/p105, p107, pRb2/p130 and simian virus-40 large T-antigen in human mesotheliomas.Nat Med 3, 913–916 (1997). https://doi.org/10.1038/nm0897-913

Download citation

This article is cited by