1887

Abstract

The established line of normal Fisher rat fibroblasts (FR3T3) is naturally resistant to the parvovirus minute virus of mice (MVM), and was used as a model system to study the influence of stepwise transformation on the susceptibility of cells to this virus. When transformed with genes encoding the class I nuclear oncoproteins large T antigen of polyomavirus (PyLT) or v-, cells retained a normal appearance, but acquired some ability to form colonies in soft agar. On the other hand, the class II transforming oncogenes encoding the middle T antigen of polyomavirus (PyMT) and c-Ha- induced both morphological alterations and a high capacity for anchorage-independent growth in transfected cells. The concomitant expression of oncogenes from both classes (PyLT+PyMT; v-+c-Ha-) induced a supertransformed phenotype characterized by the piling-up of cells into poorly adherent foci, even in low density cultures. The progressive transformation of this cellular system was found to coincide with a gradual increase in its susceptibility to MVMp (MVM prototype strain) infection. Compared to parental cells, class I, class II and double transformants proved to be sensitized to killing by MVMp to a low, moderate and large extent, respectively. Thus, oncogenes from different functional classes appeared to cooperate in the responsiveness of cells to parvovirus attack. Interestingly, this cooperation exacerbated both the killing of infected cells and their capacity to produce viral non-structural (NS) proteins, in agreement with the reported cytotoxic activity of NS polypeptides. Therefore, in this system, parameters of the parvovirus life cycle may serve as indications of the overall progression of the transformation process.

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1992-08-01
2024-04-16
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References

  1. Avalosse B., Chen Y. Q., Cornelis J., Duponchel N., Becquart P., Namba M., Rommelaere J. 1987; Amplification of parvoviral DNA as a function of host-cell transformation. In Accomplishment in Oncology vol 2 pp. 140–152 Edited by zur Hausen H., Schlehofer J. R. Philadelphia: J. B. Lippincott;
    [Google Scholar]
  2. Bodnar J. W. 1988; Sequence organization in regulatory regions of DNA of minute virus of mice. Virus Genes 2:167–182
    [Google Scholar]
  3. Brandenburger A., Legendre D., Avalosse B., Rommelaere J. 1990; NS-1 and NS-2 proteins may act synergistically in the cytopathogenicity of parvovirus MVMp. Virology 174:576–584
    [Google Scholar]
  4. Caillet-Fauquet P., Perros M., Brandenburger A., Spegelaere P., Rommelaere J. 1990; Programmed killing of human cells by means of an inducible clone of parvoviral genes encoding non-structural proteins. EMBO Journal 9:2989–2995
    [Google Scholar]
  5. Chen Y. Q., de Foresta F., Hertoghs J., Avalosse B., Cornelis J., Rommelaere J. 1986; Selective killing of simian virus 40-transformed human fibroblasts by parvovirus H-l. Cancer Research 46:3574–3579
    [Google Scholar]
  6. Cornelis J. J., Becquart P., Duponchel N., Salome N., Avalosse B., Namba M., Rommelaere J. 1988a; Transformation of human fibroblasts by ionizing radiations, a chemical carcinogen, or simian virus 40 correlates with an increase in susceptibility to the autonomous parvoviruses H1 virus and MVM. Journal of Virology 62:1679–1686
    [Google Scholar]
  7. Cornelis J. J., Spruyt N., Spegelaere P., Guetta E., Darawshi T., Cotmore S. F., Tal J., Rommelaere J. 1988b; Sensitization of transformed rat fibroblasts to killing by parvovirus minute virus of mice correlates with an increase in viral gene expression. Journal of Virology 62:3438–3444
    [Google Scholar]
  8. Cotmore S. F., Tattersall P. 1987; The autonomously replicating parvoviruses of vertebrates. Advances in Virus Research 33:91–159
    [Google Scholar]
  9. Cuzin F. 1984; Coordinated functions of three distinct proteins in the transformation of rodent cells in culture. Biochimica et biophysica acta 781:193–204
    [Google Scholar]
  10. Gelinas C., Schaffhausen B., Bockus B., Ratiarson A., Bastin M. 1989; Mutations in polyomavirus middle T antigen affecting tumorigenesis. Virology 170:193–200
    [Google Scholar]
  11. Guetta E., Mincberg M., Mousset S., Bertinchamps C., Rommelaere J., Tal J. 1990; Selective killing of transformed rat cells by minute virus of mice does not require infectious virus production. Journal of Virology 64:458–462
    [Google Scholar]
  12. Hunter T. 1991; Cooperation between oncogenes. Cell 64:249–270
    [Google Scholar]
  13. McKay I. A., Malone P., Marshall C. J., Hall A. 1986; Malignant transformation of murine fibroblasts by a human c-Ha-ras-1 oncogene does not require a functional epidermal growth factor receptor. Molecular and Cellular Biology 6:3382–3387
    [Google Scholar]
  14. Mousset S., Rommelaere J. 1982; Minute virus of mice inhibits cell transformation by simian virus 40. Nature, London 300:537–539
    [Google Scholar]
  15. Mousset S., Rommelaere J. 1988; Susceptibility to parvovirus minute virus of mice as a function of the degree of host cell transformation: little effect of simian virus 40 infection and phorbol ester treatment. Virus Research 9:107–117
    [Google Scholar]
  16. Mousset S., Cornelis J. J., Spruyt N., Rommelaere J. 1986; Transformation of established murine fibroblasts with an activated cellular Harvey-ras oncogene or the polyomavirus middle T gene increases cell permissiveness to parvovirus minute virus of mice. Biochimie 68:951–955
    [Google Scholar]
  17. Mousset S., Caillet-Fauquet P., Rommelaere J. 1991; The cytotoxicity of MVM non-structural proteins is modulated by neoplasic transformation. 4th Parvovirus Workshop, Elsinore (Denmark), August 18–22 1991 Abstract P18
    [Google Scholar]
  18. Osawa K., Ayub J., Kajigaya S., Shimada T., Young N. 1988; The gene encoding the nonstructural protein of B19 (human) parvovirus may be lethal in transfected cells. Journal of Virology 62:2884–2889
    [Google Scholar]
  19. Rameh L., Armelin M. 1991; T antigens’ role in polyomavirus transformation: c-myc but not c-fos or c-jun expression is a target for middle T. Oncogene 6:1049–1056
    [Google Scholar]
  20. Rassoulzadegan M., Cowie A., Carr A., Glaichenhaus N., Kamen R., Cuzin F. 1982; The role of individual polyomavirus early proteins in oncogenic transformation. Nature, London 300:713–718
    [Google Scholar]
  21. Rhode S. L. III 1987; Construction of a genetic switch for inducible trans-activation of gene expression in eucaryotic cells. Journal of Virology 61:1448–1456
    [Google Scholar]
  22. Rommelaere J., Cornelis J. 1991; Antineoplasic activity of parvoviruses. Journal of Virological Methods 33:237–251
    [Google Scholar]
  23. Rommelaere J., Tattersall P. 1990; Oncosuppression by parvoviruses. In Handbook of Parvoviruses vol 2 pp. 41–57 Edited by Tijssen P. Boca Raton: CRC Press;
    [Google Scholar]
  24. Ruley E. 1990; Transforming collaborations between ras and nuclear oncogenes. Cancer Cells 2:258–268
    [Google Scholar]
  25. Salome N., van Hille B., Duponchel N., Meneguzzi G., Cuzin F., Rommelaere J., Cornelis J. J. 1990; Sensitization of transformed rat cells to parvovirus MVMp is restricted to specific oncogenes. Oncogene 5:123–130
    [Google Scholar]
  26. Seif R., Cuzin F. 1977; Temperature-sensitive growth regulation in one type of transformed rat cells induced by the tsa mutant of polyomavirus. Journal of Virology 24:721–728
    [Google Scholar]
  27. Siegl G. 1984; Biology and pathogenicity of autonomous parvoviruses. In The Parvoviruses pp. 297–348 Edited by Berns K. I. New York & London: Plenum Press;
    [Google Scholar]
  28. Southern P., Berg P. 1982; Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. Journal of Molecular and Applied Genetics 1:327–341
    [Google Scholar]
  29. Spegelaere P., van Hille B., Spruyt N., Faisst S., Cornelis J., Rommelaere J. 1991; Initiation of transcription from the minute virus of mice P4 promoter is stimulated in rat cells expressing a c-Haras oncogene. Journal of Virology 65:4919–4928
    [Google Scholar]
  30. Tattersall P., Cawte P. J., Shatkin A. J., Ward D. C. 1976; Three structural polypeptides coded for by minute virus of mice, a parvovirus. Journal of Virology 20:273–289
    [Google Scholar]
  31. Treisman R., Novak U., Favaloro J., Kamen R. 1981; Transformation of rat cells by an altered polyomavirus genome expressing only the middle T protein. Nature, London 292:595–600
    [Google Scholar]
  32. van Hille B., Duponchel N., Salome N., Spruyt N., Cotmore S. F., Tattersall P., Cornelis J. J., Rommelaere J. 1989; Limitation to the expression of parvoviral nonstructural proteins may determine the extent of sensitization of E J-ras-transformed rat cells to minute virus of mice. Virology 171:89–97
    [Google Scholar]
  33. Wasylyk C., Flores P., Gutman A., Wasylyk B. V. 1989; PEA3 is a nuclear target for transcription activation by non-nuclear oncogenes. EMBO Journal 83371–3378
    [Google Scholar]
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