Nature Medicine
3, 908 - 912 (1997)
doi:10.1038/nm0897-908
Simian virus-40 large-T antigen binds p53 in human mesotheliomasMichele Carbone1, 9, Paola Rizzo1, Philip M. Grimley2, Antonio Procopio3, Daphne J.Y. Mew4, Viji Shridhar4, Andrea De Bartolomeis5, Vincenzo Esposito6, Maria Teresa Giuliano3, Seth M. Steinberg7, Arthur S. Levine8, Antonio Giordano6
& Harvey I. Pass4
1Cardinal Bemardin Cancer Center, Room 205, Cancer Immunology Program, Department of Pathology, Loyola University Chicago, 2160 South First Avenue, Maywood, Illinois 60153, USA
2Department of Pathology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland, 20889, USA
3Laboratorio di Fisiopatologia Molecolare, University ofChieti, Chieti, 66013, Italy
4Aerodigestive Program, Karmanos Cancer Institute, Detroit, Michigan 48201, USA
5Experimental Therapeutics Branch, National Institute of Mental Health, Bethesda, Maryland 20892, USA
6Deptartment of Pathology, Anatomy & Cell Biology and Sbarro Institute for Cancer Research, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA
7Biostatistics and Data Management Section, National Cancer Institute, Bethesda, Maryland 20892, USA
8Section on DNA Replication, Repair, and Mutagenesis, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA
9Correspondence should be addressed to M.C. We found that simian virus 40 (SV40) induces mesotheliomas in hamsters1 and that 60% of human mesotheiiomas contain and express SV40 sequences2, results now confirmed by others [ref. 3−5, and presentations by D. Griffiths & R. Weiss, F. Galateau-SallÈ, 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)]. Mesothelioma6−8, 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 mesothelioma6−8. 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.
REFERENCES
- Cicala, C., Pompetti, F. & Carbone, M. SV40 induces mesotheliomas in hamsters. Am. J. Pathol. 142, 1524−1533 (1993). | PubMed | ISI | ChemPort |
- Carbone, M. et al. Simian virus 40-like sequences in human pleural mesothelioma. Oncogene 9, 1781−1790 (1994). | PubMed | ISI | ChemPort |
- Cristaudo, A. et al. Molecular biology studies on mesothelioma tumor samples: Preliminary data on H-ras, p21, and SV40. J. Environ. Pathol. Toxicol. Oncol. 14, 29−34 (1995). | PubMed | ChemPort |
- Pepper, C., Jasani, B., Navabi, H., Wynford-Thomas, D. & Gibbs, A.R. Simian virus 40 large T antigen (SV40LTag) primer specific DNA amplification in human pleural mesothelioma tissue. Thorax 51, 1074−1076 (1996). | PubMed | ISI | ChemPort |
- De Luca, A. et al. Association of the retinoblastoma gene family proteins and SV40 large T-antigen in human mesotheliomas. Nature Med. 3, 913−916 (1997). | Article | PubMed | ChemPort |
- Mossman, B.T., Kamp, D. & Weitzman, S.A. Mechanisms of carcinogenesis and clinical features of asbestos-associated cancers. Cancer Invest. 14, 464−478 (1996).
- Peto, J., Hodgson, J.T., Matthews, F.E. & Jones, J. Continuing increase in mesothelioma mortality in Britain. Lancet 345, 535−539 (1995). | Article | PubMed | ISI | ChemPort |
- Carbone, M., Rizzo, P. & Pass, H.I. Simian Virus 40, Pdliovaccines, and Human Tumors: A Review of Recent Developments. Oncogene. (in the press)
- Carbone, M. et al. SV40-like sequences in human bone tumors. Oncogene 13, 527−535 (1996). | PubMed | ISI | ChemPort |
- Lednicky, J.A., Garcea, R.L., Bergsagel, D.J. & Butel, J.S. Natural simian virus 40 strains are present in human choroid plexus and ependymoma tumors. Virology 212, 710−717 (1995). | Article | PubMed | ISI | ChemPort |
- Lednicky, J.A., Stewart, A.R., Jenkins, J.J., III, Finegold, M.J. & Butel, J.S. SV40 DNA in human osteosarcomas shows sequence variation among T-antigen genes. Int. J. Cancer (in the press).
- Bergsagel, D.J., Finegold, M.J., Butel, J.S., Kupsky, W.J. & Garcea, R. DNA sequences similar to those of simian virus 40 in ependymomas and choroid plexus tumors of childhood. N. Engl. J. Med. 36, 988−993 (1992).
- Martini, F. et al Simian virus 40 early region and large T antigen in human brain tumors, peripheral blood cells, and sperm fluids from healthy individuals. Cancer Res. 56, 4820−4825 (1996). | PubMed | ISI | ChemPort |
- Strickler, H.D. et al. Simian virus 40 and pleural mesothelioma in humans. Cancer Epidemiol. Biostatist. Prevent. 5, 473−475 (1995).
- Jensen, F., Koprowski, H., Pagano, J.S., Ponten, J. & Ravdin, R.G. Autologous and homologous implantation of human cells transformed in vitro by SV40. J. Natl. Cancer Inst. 32, 917−937 (1964).
- Avantaggiati, M.L., Carbone, M., Graessmann, A., Howard, B. & Levine, A.S. The SV40 large T antigen and Adenovirus E1 A oncoproteins interact with different isoforms of the transcriptional coactivator, p300. EMBO J. 15, 2236−2248 (1996). | PubMed | ISI | ChemPort |
- Simmons, D.T. Transformation by polyomaviruses: Role of tumor suppressor proteins. in: DNA Tumor Viruses: Oncogenic Mechanisms. (eds. Barbanti Brodano, G., Bendinelli, M. & Friedman, H.) 27−50 (Plenum, New York & London, 1995). | ChemPort |
- Tiemann, F., Zerrhan, J. & Deppert, W. Cooperation of simian virus 40 large and small T antigens in metabolic stabilization of tumor suppressor p53 during cellular transformation. J. Virol. 69, 6115−6121 (1995). | PubMed | ISI | ChemPort |
- Metha, C.R., Patel, N.R. & Tsiatis, A.A. Exact significance testing establishing treatment equivalent with ordered categorical data. Biometrics 40, 819−825 (1984). | PubMed |
- Mayall, F.G., Goddard, H. & Gibbs, A.R. The frequency of p53 immunostaining in asbestos-associated mesotheliomas and non-asbestos associated mesotheliomas. Histopathology 22, 383−386 (1993). | PubMed | ISI | ChemPort |
- Metcalf, R. et al. p53 and Kirsten-ras mutations in human mesothelioma cell lines. Cancer Res. 52, 2610−2615 (1992). | PubMed | ISI | ChemPort |
- Andersson, M. et al. Lung carcinoma and malignant mesothelioma in patients exposed to Thorotrast: Incidence, histology, and p53 status. Int. J. Cancer. 63, 330−336 (1995). | PubMed | ISI | ChemPort |
- Greenblatt, M.S., Bennett, W.P., Hollstein, M. & Harris, C.C. Mutations in the p53 tumor suppressor gene: Clues to cancer etiology and molecular pathogenesis. Cancer Res. 54, 4855−4878 (1994). | PubMed | ISI | ChemPort |
- Ruley, H.E. p53 and response to chemotherapy and radiotherapy. in: Important Advances in Oncology. (eds. De Vita, V.T., Jr., Hellman S. & Rosenberg, S.A.) 37−56 (Lippincott, Philadelphia, 1996). | ChemPort |
- Buchman, V.L., Chumakov, P.M., Ninkina, N.N., Samarina, O.P. & Georgiev, G.P. A variation in the structure of the protein-coding region of the human p53 gene. Gene 70, 245−252 (1988). | Article | PubMed | ISI | ChemPort |
- Marshall, J., Smith, A.E. & Cheng, S.H. Monoclonal antibody specific for BK virus large-T antigen allows discrimination among the different papovaviral large-T antigens. Oncogene 6, 1673−1676 (1991). | PubMed | ISI | ChemPort |
- Frost, J.A. et al. Simian virus 40 small t antigen cooperates with mitogen activated kinases to stimulate AP-1 activity. Mol. Cell. Biol. 14, 6244−6252 (1994). | PubMed | ISI | ChemPort |
- Heintz, N.H., Janssen, Y.M. & Mossman, B.T. Persistent induction of c-fos and c-jun protooncogene expression by asbestos. Proc. Natl. Acad. Sci. USA 90, 3299−3304 (1993). | PubMed | ChemPort |
- Cicala, C. et al. SV40 small t deletion mutants preferentially transform mononuclear phagocytes and B-lymphocytes in vivo. Virology 190, 475−479 (1992). | Article | PubMed | ISI | ChemPort |
- Cicala, C. et al. Simian virus 40 small-t antigen stimulates viral DNA replication in permissive monkey cells. J. Virol. 68, 3138−3144 (1994). | PubMed | ISI | ChemPort |
- Michieli, P. et al. Induction of Wafl/Cipl by a p53-independent pathway. Cancer Res. 54, 3391−3395 (1994). | PubMed | ISI | ChemPort |
- Ewald, D. et al. Time-sensitive reversal of hyperplasia in transgenic mice expressing SV40 T antigen. Science 273, 1384−1386 (1996). | PubMed | ISI | ChemPort |
- Moorwood, K., Price, T.N.C. & Mayne, L.V. Mutation of p53 is not a prerequisite for immortalization of human fibroblasts by SV40 T antigen. Exp. Cell Res. 223, 308−313 (1996). | Article | PubMed | ISI | ChemPort |
- Banga, S.S. et al. SEN6, a locus for SV40 mediated immortalization of human cells, maps to 6q26−27. Oncogene 14, 313−321 (1997). | Article | PubMed | ISI | ChemPort |
- Maroulakaou, I.G., Anver, M., Garrett, L. & Green, J.E. Prostate and mammary adenocarcinoma in transgenic mice carrying a rat C3 (1) simian virus 40 large tumor antigen fusion gene. Proc. Natl. Acad. Sci. USA 91, 11236−11240 (1994). | PubMed | ChemPort |
- Reddel, R.R., Malan-Shibley, L., Gerwin, B.I., Metcalf, R.A. & Harris, C.C. Tumorigenicity of human mesothelial cell line transfected with EJ-ras oncogene. J Natl. Cancer Inst. 81, 945−948 (1989). | PubMed | ChemPort |
- Appel, J.D., Fasy, T.M., Kohtz, D.S. & Johnson, E.M. Asbestos fibers mediate transformation of monkey cells by exogenous plasmid DNA. Proc. Natl. Acad. Sci. USA 85, 7670−7674 (1988). | PubMed | ChemPort |
- Dubes, G.R. Asbestos mediates viral DNA transformation of mouse cells to produce multilayered foci (abstract). Proc. Am. Assoc. Cancer Res. 34, 185 (1993).
- Marsella, J.M., Liu, B.L., Vaslet, C.A. & Agnes, B.K. Susceptibility of p53-deficient mice to induction of mesothelioma by crocidolite asbestos fibers. Environ. Health Perspect. (in the press).
- Pompetti, F. et al. Oncogene alterations in primary, recurrent, and metastatic human bone tumors. J. Cell. Biochem. 63, 37−50 (1996). | Article | PubMed | ISI | ChemPort |
- Lehman, T.A. et al. p53 mutations, ras mutations and p53-heat-shock protein complexes in human lung carcinoma cell lines. Cancer Res. 51, 4090−4096 (1991). | PubMed | ISI | ChemPort |
- de Bartolomeis, A. et al. Dopaminergic and peptidergic mRNA levels in juvenile rat brain after prenatal cocaine treatment. Brain Res. Mol. Brain. Res. 21, 312−332 (1994). | PubMed |
|
