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DNA Tumor Viruses pp 15–26Cite as

Simian Virus 40 Large T Antigen Induces Chromosome Damage that Precedes and Coincides with Complete Neoplastic Transformation

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Abstract

In the early 1900s, Theodor Boveri made some rather remarkable predictions.(1) On the basis of his observations of mitoses in sea urchin eggs, he postulated the involvement of abnormal chromosomes in oncogenesis and even postulated the existence of “chromosomes which inhibit division.” Such early work laid the foundation for the theory that tumorigenesis is a series of genetic mutations. In the early 1980s, actual mutations in growth regulatory genes, termed oncogenes, were described.(2,3) Pairs of oncogenes deregulated by mutation were found sufficient to induce tumorigenesis in rodent cells.(4,5) Then negative regulators of cell growth, the antithesis of the oncogenes, called tumor suppressor genes received renewed and intense attention on identification of the retinoblastoma gene.(6,7) It is now clear that the loss of function of tumor suppressor genes is as important, if not more so, in the tumor-forming process than the activation of oncogenes.(8–12) Thus, recently, heritable changes have been found at the level of single-base-pair changes that, when combined to form a sufficient cadre of changes, enable a cell to become deregulated to the point of autonomy.

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References

  1. Boveri, T., 1914, Zur Frage der Entstehung Maligner Tumoren, Gustav Fischer, Jena.

    Google Scholar 

  2. Cooper, G. M., 1982, Cellular transforming genes, Science 218:801–806.

    Article  Google Scholar 

  3. Bishop, J. M., 1983, Cellular oncogenes and retroviruses, Annu. Rev. Biochem. 52:301–354.

    Article  PubMed  CAS  Google Scholar 

  4. Land, H., Parada, L. F., and Weinberg, R. A., 1983, Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes, Nature 304:596–602.

    Article  PubMed  CAS  Google Scholar 

  5. Ruley, E. H., 1983, Adenovirus early region 1A enables viral and cellular transforming genes to transform primary cells in culture, Nature 304:602–606.

    Article  PubMed  CAS  Google Scholar 

  6. Knudson, A. G., 1985, Hereditary cancer, oncogenes, and antioncogenes, Cancer Res. 45:1437–1443.

    PubMed  CAS  Google Scholar 

  7. Klein, G., 1987, The approaching era of the tumor suppressor genes, Science 238:1539–1545.

    Article  PubMed  CAS  Google Scholar 

  8. Baker, S. J., Fearon, E. R., Nigro, J. M., Hamilton, S. R., Preisinger, A. C., Jessup, J. M., van Tuinen, P., Ledbetter, D. H., Barker, D. E., Nakamura, Y., White, R., and Vogelstein, B., 1989, Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas, Science 244:217–221.

    Article  PubMed  CAS  Google Scholar 

  9. Vogelstein, B., Fearon, E. R., Kern, S. E., Hamilton, S. R., Preisinger, A. C., Nakumura, Y., and White, R., 1989, Allelotype of colorectal carcinomas, Science 244:207–211.

    Article  PubMed  CAS  Google Scholar 

  10. Fearon, E. R., Cho, K. R., Nigro, J. M., Kern, S. E., Simons, J. W., Ruppert, J. M., Hamilton, S. R., Preisinger, A. C., Thomas, G., Kinzler, K. W., and Vogelstein, B., 1990, Identification of a chromosome 18q gene that is altered in colorectal cancers, Science 247:49–56.

    Article  PubMed  CAS  Google Scholar 

  11. Vogelstein, B., 1990, A deadly inheritance, Nature 348:681–682.

    Article  PubMed  CAS  Google Scholar 

  12. Hollstein, M., Sidransky, D., Vogelstein, B., and Harris, C. C., 1991, p53 mutations in human cancers, Science 253:49–53.

    Article  PubMed  CAS  Google Scholar 

  13. McBride, O. W., Merry, D., and Givol, D., 1986, The gene for human p53 cellular tumor antigen is located on chromosome 17 short arm (17p13), Proc. Natl Acad. Sci. USA 83:130–134.

    Article  PubMed  CAS  Google Scholar 

  14. Kastan, M. B., Onyekwere, O., Sidransky, D., Vogelstein, B., and Craig, R. W., 1991, Participation of p53 protein in the cellular response to DNA damage, Cancer Res. 51:6304–6311.

    PubMed  CAS  Google Scholar 

  15. Kuerbitz, S. J., Plunkett, B. S., Walsh, W. V., and Kastan, M. B., 1992, Wild-type p53 is a cell cycle checkpoint determinant following irradiation, Proc. Natl. Acad. Sci. USA 89:7491–7495.

    Article  PubMed  CAS  Google Scholar 

  16. Bakalkin, G., Yakovleva, T., Seiivanova, G., Magnusson, K. P., Szekely, L., Kiseleva, E., Klein, G., Terenius, L., and Wiman, K. G., 1994, p53 binds single-stranded DNA ends and catalyzes DNA renaturation and strand transfer, Proc. Natl. Acad. Sci. USA 91:413–417.

    Article  PubMed  CAS  Google Scholar 

  17. Nowell, P. C., 1976, The clonal evolution of tumor cell populations, Science 194:23–28.

    Article  PubMed  CAS  Google Scholar 

  18. Freedman, V. H., and Shin, S.-I., 1974, Cellular tumorigenicity in nude mice: Correlation with cell growth in semi-solid medium, Cell 3:355–359.

    Article  PubMed  CAS  Google Scholar 

  19. Dulbecco, R., 1970, Topoinhibition and serum requirement of transformed and untrans-formed cells, Nature 227:802–806.

    Article  PubMed  CAS  Google Scholar 

  20. Folkman, J., Watson, K., Ingber, D., and Hanahan, D., 1989, Induction of angiogenesis during the transition from hyperplasia to neoplasia, Nature 339:58–61.

    Article  PubMed  CAS  Google Scholar 

  21. Fidler, I. J., 1990, Critical factors in the biology of human cancer metastasis: Twenty-eighth G. H. A. Clowes Memorial Award Lecture, Cancer Res. 50:6130–6138.

    PubMed  CAS  Google Scholar 

  22. German, J. (ed.), 1983, Chromosome Mutation and Neoplasia, Alan R. Liss, New York.

    Google Scholar 

  23. de Klein, A., van Kessel, A. G., Grosveld, G., Bartram, C. R., Hagemeijer, A., Bootsma, D., Spurr, N. K., Heisterkamp, N., Groffen, J., and Stephenson, J. R., 1982, A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemia, Nature 300:765–767.

    Article  PubMed  Google Scholar 

  24. Croce, C. M., 1986, Chromosome translocations and human cancer, Cancer Res. 46:6019–6023.

    PubMed  CAS  Google Scholar 

  25. Eddy, B. E., Borman, G. S., Grubbs, G. E., and Young, R. D., 1962, Identification of the oncogenic substance in rhesus monkey kidney cell cultures as simian virus 40, Virology 17:65–75.

    Article  PubMed  CAS  Google Scholar 

  26. Koprowski, H., Ponten, J. A., Jensen, E., Raudin, R. G., Moorhead, P., and Saksela, E., 1962, Transformation of human tissue infected with simian virus 40, J. Cell. Comp. Physiol. 59:281–292.

    Article  Google Scholar 

  27. Wolman, S. R., Hirschhorn, K., and Todaro, G. J., 1964, Early chromosomal changes in SV40-infected human fibroblast cultures, Cytogenetics 3:45–61.

    Article  PubMed  CAS  Google Scholar 

  28. Huschtscha, L. I., and Holliday, R., 1983, Limited and unlimited growth of SV40-transformed cells from human diploid MRC-5 fibroblasts, J. Cell Sci. 63:77–99.

    PubMed  CAS  Google Scholar 

  29. Soriano, F., Shelburne, C. E., and Gokcen, M., 1974, Simian virus 40 in a human cancer, Nature 249:421–424.

    Article  PubMed  CAS  Google Scholar 

  30. Bergsagel, D. J., Finegold, M. J., Butel, J. S., Kupsky, W. J., and Garcea, R. L., 1992, DNA sequences similar to those of simian virus 40 in ependymomas and choroid plexus tumors of childhood, N. Engl.J. Med. 326:988–993.

    Article  PubMed  CAS  Google Scholar 

  31. Carbone, M., Pass, H. I., Rizzo, P., Marinetti, M., Di Muzio, M., Mew, D. J., Levine, A. S., and Procopio, A., 1994, Simian virus 40-like DNA sequences in human pleural mesothelioma, Oncogene 9:1781–1790.

    PubMed  CAS  Google Scholar 

  32. Topp, W. C., Lane, D., and Pollack, R., 1980, Transformation by SV40 and polyoma virus, in: DNA Tumor Viruses, 2nd ed., part 2 (J. Tooze, ed.), Cold Spring Harbor Laboratory, New York, pp. 205–296.

    Google Scholar 

  33. Li, J. J., and Kelly, T. J., 1984, Simian virus 40 DNA replication in vitro. Proc. Natl Acad. Sci. USA 81:6973–6977.

    Article  PubMed  CAS  Google Scholar 

  34. Kelly, T. J., 1988, SV40 DNA replication, J. Biol. Chem. 263:17889–17892.

    PubMed  CAS  Google Scholar 

  35. Noble, J. C., Pan, Z. Q., Prives, C., and Manley, J. L., 1987, Splicing of SV40 early pre-mRNA to large T and small t mRNAs utilizes different patterns of lariat branch sites, Cell 50:227–236.

    Article  PubMed  CAS  Google Scholar 

  36. Fu, X.-Y., and Manley, J. L., 1987, Factors influencing alternative splice site utilization in vivo, Mol. Cell. Biol. 7:738–748.

    PubMed  CAS  Google Scholar 

  37. Major, E. O., and Matsumura, P., 1984, Human embryonic kidney cells: Stable transformation with an origin-defective simian virus 40 DNA and use as hosts for human papovavirus replication, Mol. Cell. Biol. 4:379–382.

    PubMed  CAS  Google Scholar 

  38. Murnane, J. P., Fuller, L. F., and Painter, R. B., 1985, Establishment and characterization of a permanent pSV ori-transformed ataxia-telangiectasia cell line, Exp. Cell Res. 158:119–126.

    Article  PubMed  CAS  Google Scholar 

  39. Canaani, D., Naiman, T., Teitz, T., and Berg, P., 1986, Immortalization of xeroderma pigmen-tosum cells by simian virus 40 DNA having a defective origin of DNA replication, Somat. Cell Mol Genet. 12:13–20.

    Article  PubMed  CAS  Google Scholar 

  40. Daya-Grosjean, L., James, M. R., Drougard, C., and Sarasin, A., 1987, An immortalized xeroderma pigmentosum, group C., cell line which replicates SV40 shuttle vectors, Mut. Res. 183:185–196.

    Article  CAS  Google Scholar 

  41. Neufeld, D. S., Ripley, S., Henderson, A., and Ozer, H. L., 1987, Immortalization of human fibroblasts transformed by origin-defective simian virus 40, Mol. Cell. Biol. 7:2794–2802.

    PubMed  CAS  Google Scholar 

  42. Chang, L.-S., Pater, M. M., Hutchinson, N. I., and Di Mayorca, G., 1984, Transformation by purified early genes of simian virus 40, Virology 133:341–353.

    Article  PubMed  CAS  Google Scholar 

  43. Chang, L.-S., Pan, S., Pater, M. M., and Di Mayorca, G., 1985, Differential requirement for SV40 early genes in immortalization and transformation of primary rat and human embryonic cells, Virology 146:246–261.

    Article  PubMed  CAS  Google Scholar 

  44. Chang, P. L., Gunby J. L., Tomkins, DJ., Mak, I., Rosa, N. E., and Mak, S., 1986, Transformation of human cultured fibroblasts with plasmids carrying dominant selection markers and immortalizing potential, Exp. Cell Res. 167:407–416.

    Article  PubMed  CAS  Google Scholar 

  45. Mayne, L. V., Priestley, A., James, M. R., and Burke, J. F., 1986, Efficient immortalization and morphological transformation of human fibroblasts by transfection with SV40 DNA linked to a dominant marker, Exp. Cell Res. 162:530–538.

    Article  PubMed  CAS  Google Scholar 

  46. Wood, C. M., Timme, T. L., Hurt, M. M., Brinkley, B. R., Ledbetter, D. H., and Moses, R. E., 1987, Transformation of DNA repair-deficient human diploid fibroblasts with a simian virus 40 plasmid, Exp. Cell Res. 169:543–553.

    Article  PubMed  CAS  Google Scholar 

  47. Zouzias, D., Jha, K. K., Mulder, C., Basilico, C., and Ozer, H. L., 1980, Human fibroblasts transformed by the early region of SV40 DNA: Analysis of “free” viral DNA sequences, Virology 104:439–453.

    Article  PubMed  CAS  Google Scholar 

  48. Gotoh, S., Gelb, L., and Schlessinger, D., 1979, SV40-transformed human diploid cells that remain transformed throughout their limited lifespan. J. Gen. Virol. 42:409–414.

    Article  PubMed  CAS  Google Scholar 

  49. Ray, F. A., Peabody, D. S., Cooper, J. L., Cram, L. S., and Kraemer, P. M., 1990, SV40 T antigen alone drives karyotype instability that precedes neoplastic transformation of human diploid fibroblasts, J. Cell. Biochem. 42:13–31.

    Article  PubMed  CAS  Google Scholar 

  50. Gorman, C. M., Merlino, G. T., Willingham, M. C., Pastan, I., and Howard, B. H., 1982, The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection, Proc. Natl Acad. Sci. USA 79:6777–6781.

    Article  PubMed  CAS  Google Scholar 

  51. Shenk, T. E., Carbon, J., and Berg, P., 1976, Construction and analysis of viable deletion mutants of simian virus 40, J. Virol. 18:664–671.

    PubMed  CAS  Google Scholar 

  52. Kraemer, P. M., Travis, G. L., Ray, F. A., and Cram, L. S., 1983, Spontaneous neoplastic evolution of Chinese hamster cells in culture: Multistep progression of phenotypes, Cancer Res. 43:4822–4827.

    PubMed  CAS  Google Scholar 

  53. Stewart, N., and Bacchetti, S., 1991, Expression of SV40 large T antigen, but not small t antigen, is required for the induction of chromosomal aberrations in transformed human cells, Virology 180:49–57.

    Article  PubMed  CAS  Google Scholar 

  54. Zerrahn, J., Knippschild, U., Winkler, T., and Deppert, W., 1993, Independent expression of the transforming amino-terminal domain of SV40 large T antigen from an alternatively spliced third SV40 early mRNA, EMBOJ. 12:4739–4746.

    CAS  Google Scholar 

  55. de Ronde, A., Sol, C.J., van Strien, A., ter Schegget J., and van der Noordaa J., 1989, The small t antigen is essential for the morphological transformation of human fibroblasts, Virol. 171:260–263.

    Article  Google Scholar 

  56. Ray, F. A., and Kraemer, P. M., 1993, Iterative chromosome mutation and selection as a mechanism of complete transformation of human diploid fibroblasts by SV40 T antigen, Carcinogenesis 14:1511–1516.

    Article  PubMed  CAS  Google Scholar 

  57. Shay, J. W., Pereira-Smith, O. M., and Wright, W. E., 1991, A role for both RB and p53 in the regulation of human cellular senescence, Exp. Cell Res. 196:33–39.

    Article  PubMed  CAS  Google Scholar 

  58. Lin, J.-Y., and Simmons, D. T., 1991, The ability of large T antigen to complex with p53 is necessary for the increased lifespan and partial transformation of human cells by simian virus 40, J. Virol. 65:6447–6453.

    PubMed  CAS  Google Scholar 

  59. Stein, G. H., 1985, SV40-transformed human fibroblasts: Evidence for cellular aging in precrisis cells, J. Cell. Physiol. 125:36–44.

    Article  PubMed  CAS  Google Scholar 

  60. Ray, F. A., Meyne, J., and Kraemer, P. M., 1992, SV40 T antigen induced chromosomal changes reflect a process that is both clastogenic and aneuploidogenic and is ongoing throughout neoplastic progression of human fibroblasts, Mut. Res. 284:265–273.

    Article  CAS  Google Scholar 

  61. Shay, J. W., and Wright, W. E., 1989, Quantitation of the frequency of immortalization of normal human diploid fibroblasts by SV40 large T-antigen, Exp. Cell Res. 184:109–118.

    Article  PubMed  CAS  Google Scholar 

  62. Norwood, T. H., Pendergrass, W. R., Sprague, C. A., and Martin, G. M., 1974, Dominance of the senescent phenotype in heterokaryons between replicative and post-replicative human fibroblast-like cells, Proc. Natl. Acad. Sci. USA 71:2231–2235.

    Article  PubMed  CAS  Google Scholar 

  63. Goldstein, S., 1990, Replicative senescence: The human fibroblast comes of age, Science 249:1129–1133.

    Article  PubMed  CAS  Google Scholar 

  64. McCormick, J. J., and Maher, V. M., 1989, Malignant transformation of mammalian cells in culture, including human cells, Environ. Mol. Mutagen. 16:105–113.

    Article  Google Scholar 

  65. Levine, A. J., and Momand, J., 1990, Tumor suppressor genes: The p53 and retinoblastoma sensitivity genes and gene products, Biochim. Biophys. Acta 1032:119–136.

    PubMed  CAS  Google Scholar 

  66. Loeb, L. A., 1991, Mutator phenotype may be required for multistage carcinogenesis, Cancer Res. 51:3075–3079.

    PubMed  CAS  Google Scholar 

  67. Ray, F. A., and Kraemer, P. M., 1992, Frequent deletions in nine newly immortal human cell lines, Cancer Genet. Cytogenet. 59:39–44.

    Article  PubMed  CAS  Google Scholar 

  68. Hubbard-Smith, K., Patsalis, P., Pardinas, J. R., Jha, K. K., Henderson, A. S., and Ozer, H. L., 1992, Altered chromosome 6 in immortal human fibroblasts, Mol Cell. Biol. 12:2273–2281.

    PubMed  CAS  Google Scholar 

  69. Kraemer, P. M., Travis, G. L., Saunders, G. C., Ray, F. A., Stevenson, A. P., Bame, K., and Cram, L. S., 1984, Tumorigenicity assays in nude mice: Analysis of the implanted gelatin sponge method, in: Immune-Deficient Animals (B. Sordat, ed.), S. Karger, Basel, pp. 214–219.

    Google Scholar 

  70. Rhim, J. S., Jay, G., Arnstein, P., Price, F. M., Sanford, K. K., and Aaronson, S. A., 1985, Neoplastic transformation of human epidermal keratinocytes by Adl2-SV40 and Kirsten sarcoma viruses, Science 227:1250–1252.

    Article  PubMed  CAS  Google Scholar 

  71. Rhim, J. S., Fujita, J., Arnstein, P., and Aaronson, S. A., 1986, Neoplastic conversion of human keratinocytes by adenovirus 12-SV40 virus and chemical carcinogens, Science 232:385–388.

    Article  PubMed  CAS  Google Scholar 

  72. Gorbunova, L. V., Varshaver, N. B., Marshak, M. I., and Shapiro, N. I., 1982, The role of the transforming A gene of SV40 in the mutagenic activity of the virus, Mol. Gen. Genet. 187:473–476.

    Article  PubMed  CAS  Google Scholar 

  73. Liu, J., Li, H., Nomura, K., Dofuku, R., and Kitagawa, T., 1991, Cytogenetic analysis of hepatic cell lines derived form SV40-T antigen gene-harboring transgenic mice, Cancer Genet. Cytogenet. 55:207–216.

    Article  PubMed  CAS  Google Scholar 

  74. Levine, A. J., 1990, The p53 protein and its interactions with the oncogene products of the small DNA tumor viruses, Virology 177:419–426.

    Article  PubMed  CAS  Google Scholar 

  75. Levine, A. J., 1993, The tumor suppressor genes, Annu. Rev. Biochem. 62:623–651.

    Article  PubMed  CAS  Google Scholar 

  76. Dodson, M., Dean, F. B., Bullock, P., Echols, H., and Hurwitz, J., 1987, Unwinding of duplex DNA from the SV40 origin of replication by T antigen, Science 238:964–967.

    Article  PubMed  CAS  Google Scholar 

  77. Borowiec, J. A., Dean, F. B., Bullock, P. A., and Hurwitz, J., 1990, Binding and unwinding—How T antigen engages the SV40 origin of replication, Cell 60:181–184.

    Article  PubMed  CAS  Google Scholar 

  78. Gruss, C., Wetzel, E., Baack, M., Mock, U., and Knippers, R., 1988, High-affinity SV40 T-antigen binding sites in the human genome, Virology 167:349–360.

    PubMed  CAS  Google Scholar 

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  1. F. Andrew Ray

    Present address: Department of Microbiology, Immunology and Molecular Genetics, The Albany Medical College, Albany, New York, 12208-3479, USA

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  1. Life Sciences Division, Los Alamos National Laboratory, Los Alamos, New Mexico, 87545, USA

    F. Andrew Ray

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  1. Institute of Microbiology, School of Medicine, University of Ferrara, I-44100, Ferrara, Italy

    Giuseppe Barbanti-Brodano

  2. University of Pisa, Pisa, Italy

    Mauro Bendinelli

  3. University of South Florida, Tampa, Florida, USA

    Herman Friedman

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Ray, F.A. (1995). Simian Virus 40 Large T Antigen Induces Chromosome Damage that Precedes and Coincides with Complete Neoplastic Transformation. In: Barbanti-Brodano, G., Bendinelli, M., Friedman, H. (eds) DNA Tumor Viruses. Infectious Agents and Pathogenesis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1100-1_2

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