1887

Abstract

The close association between human papillomavirus type 16 (HPV-16) and cervical cancer implies some role for the virus in the development of this disease. Recent studies have shown that HPV-16, under the control of strong heterologous promoters, can cooperate with the activated oncogene to transform primary baby rat kidney cells. Virus types associated with benign lesions, e.g. HPV-6 and -11, do not function in this system. The discrimination between virus types associated with benign and tumorigenic lesions by this assay implicate it as a useful system for the study of transformation The studies reported here investigate the activity of the HP V -16 early gene product E2 in transformation. In the presence of exogenous E2, endogenous viral promoters are stimulated sufficiently to give a high efficiency of transformation in primary epithelial cells. This transactivation by E2 obviates the need for heterologous promoters, and implicates increased viral gene expression as a prerequisite for transformation. The stimulatory effect of E2 appears to be mediated through increased levels of expression of the E7 protein, which has been shown in similar assays to be sufficient to give transformation in cooperation with CAT assays confirm that HPV-16 E2 can transactivate the HPV-16 early promoters. These studies demonstrate some of the elements in a complex series of events likely to be involved in the development of cervical carcinomas.

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1990-01-01
2024-03-29
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References

  1. Ahola H., Stenlund A., Moreno-Lopez J., Pettersson U. 1987; Promoters and processing sites within the transforming region of bovine papillomavirus type 1. Journal of Virology 61:2240–2244
    [Google Scholar]
  2. Androphy E. J., Hubbert N. L., Schiller J. T., Lowy D. R. 1987; Identification of the HPV-16 E6 protein from transformed mouse cells and human cervical carcinoma cell lines. EMBO Journal 6:989–992
    [Google Scholar]
  3. Baker C. C., Phelps W. C., Lindgren V., Braun M. J., Gonda M. A., Howley P. M. 1987; Structural and transcriptional analysis of human papillomavirus type 16 sequences in cervical carcinoma cell lines. Journal of Virology 61:962–971
    [Google Scholar]
  4. Bonner W. M., Laskey R. A. 1974; A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels. European Journal of Biochemistry 46:83–88
    [Google Scholar]
  5. Brent R., Ptashne M. 1985; A eukaryotic transcriptional factor bearing the DNA specificity of a prokaryotic repressor. Cell 43:729–736
    [Google Scholar]
  6. Chin M. T., Hirochika H., Hirochika R., Broker T. R., Chow L. T. 1988; Regulation of human papillomavirus type 11 enhancer and E6 promoter by activating and repressing proteins from the E2 open reading frame: functional and biochemical studies. Journal of Virology 62:2994–3002
    [Google Scholar]
  7. Chirgwin J., Przybyla A. E., Macdonald R. C., Rutter W. J. 1979; Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18:5294–5299
    [Google Scholar]
  8. Choe J., Vaillancourt P., Stenlund A., Botchan M. 1989; Bovine papillomavirus type 1 encodes two forms of a transcriptional repressor: structural and functional analysis of new viral cDNAs. Journal of Virology 63:1743–1755
    [Google Scholar]
  9. Cripe T. P., Haugen T. H., Turk J., Tabatabai F., Schmid P. G., Dürst M., Gissmann L., Roman A., Turek L. P. 1987; Transcriptional regulation of the human papillomavirus-16 E6-E7 promoter by a keratinocyte-dependent enhancer, and by viral E2 trans-activator and repressor gene products: implications for cervical carcinogenesis. EMBO Journal 6:3743–3751
    [Google Scholar]
  10. Crook T., Storey A., Almond N., Osborn K., Crawford L. 1988; Human papillomavirus type 16 cooperates with activated ras and fos oncogenes in the hormone-dependent transformation of primary mouse cells. Proceedings of the National Academy of Sciences, U.S.A 85:8820–8824
    [Google Scholar]
  11. Crook T., Morgenstern J., Crawford L., Banks L. 1989; Continued expression of HPV-16 E7 protein is required for maintenance of the transformed phenotype of cells cotransformed by HPV-16 plus EJ-ras . EMBO Journal 8:513–519
    [Google Scholar]
  12. Dartmann K., Schwartz E., Gissmann L., Zur Hausen H. 1986; The nucleotide sequence and genome organization of human papillomavirus type 11. Virology 151:124–130
    [Google Scholar]
  13. De Villiers E. M., Schneider A., Miklaw H., Papendick U., Wagner D., Wesch H., Wahrendorf J., Zur Hausen H. 1987; Human papillomavirus infections in women with and without abnormal cervical cytology. Lancet ii:703–706
    [Google Scholar]
  14. Dimaio D., Settleman J. 1988; Bovine papillomavirus mutant temperature sensitive for transformation, replication, and trans-activation. EMBO Journal 7:1197–1204
    [Google Scholar]
  15. Dürst M., Gissmann L., Ikenberg H., Zur Hausen H. 1983; A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. Proceedings of the National Academy of Sciences, U.S.A 80:3812–3815
    [Google Scholar]
  16. Gergely L., Czegledy J., Hernady Z. 1987; Human papillomavirus frequency in normal cervical tissue. Lancet ii:513
    [Google Scholar]
  17. Giri I., Yaniv M. 1988; Structural and mutational analysis of E2 trans-activating proteins of papillomaviruses reveals three distinct functional domains. EMBO Journal 7:2823–2829
    [Google Scholar]
  18. Giri I., Danos O., Thierry F., George E., Orth G., Yaniv M. 1985; Characterization of transcription control regions of the cottontail rabbit papillomavirus. UCLA Symposia on Molecular and Cellular Biology 32:379–390
    [Google Scholar]
  19. Gissmann L., Wolnick L., Ikenberg H., Koldovsky V., Schnurch H., Zur Hausen H. 1983; Human papillomavirus types 6 and 11 DNA sequences in genital and laryngeal papillomas and in some cervical cancers. Proceedings of the National Academy of Sciences, U.S.A 80:560–563
    [Google Scholar]
  20. Gloss B., Bernard H. U., Seedorf K., Klock G. 1987; The upstream regulatory region of the human papillomavirus-16 contains an E2 protein-independent enhancer which is specific for cervical carcinoma cells and regulated by glucocorticoid hormones. EMBO Journal 6:3735–3743
    [Google Scholar]
  21. Gloss B., Chong T., Bernard H. U. 1989; Numerous nuclear proteins bind the long control region of human papillomavirus type 16: a subset of 6 of 23 DNase I-protected segments coincides with the location of the cell-type-specific enhancer. Journal of Virology 63:1142–1152
    [Google Scholar]
  22. Gorman C. M., Moffat L. F., Howard B. H. 1982; Recombinant genomes which express chloramphenicol acetyl-transferase in mammalian cells. Molecular and Cellular Biology 2:1044–1051
    [Google Scholar]
  23. Haugen T. H., Cripe T. P., Ginder G. D., Karin M., Turek L. P. 1987; Trans-activation of an upstream early gene promoter of bovine papillomavirus-1 by a product of the viral E2 gene. EMBO Journal 6:145–152
    [Google Scholar]
  24. Haugen T. H., Turek L. P., Mercurio F. M., Cripe T. P., Olson B. J., Anderson R. D., Seidi D., Karin M., Schiller J. 1988; Sequence-specific and general transcriptional activation by the bovine papillomavirus-1 E2 trans-activator require an N-terminal amphipathic helix-containing E2 domain. EMBO Journal 7:4245–4253
    [Google Scholar]
  25. Hawley-Nelson P., Androphy E. J., Lowy D. R., Schiller J. T. 1988; The specific DNA recognition sequence of the bovine papillomavirus E2 protein is an E2-dependent enhancer. EMBO Journal 7:525–531
    [Google Scholar]
  26. Hermonat P. L., Spalholz B. A., Howley P. M. 1988; The bovine papillomavirus P2443 promoter is E2 transresponsive: evidence for E2 autoregulation. EMBO Journal 7:2815–2822
    [Google Scholar]
  27. Hirochika H., Broker T. R., Chow L. T. 1987; Enhancers and trans-acting E2 transcriptional factors of papillomaviruses. Journal of Virology 61:2599–2606
    [Google Scholar]
  28. Hope I. A., Struhl K. 1986; Functional dissection of a eukaryotic transcriptional activator protein GCN4 of yeast. Cell 46:885–894
    [Google Scholar]
  29. Hubbert N. L., Schiller J. T., Lowy D. R., Androphy E. J. 1988; Bovine papilloma virus-transformed cells contain multiple E2 proteins. Proceedings of the National Academy of Sciences, U.S.A 85:5864–5868
    [Google Scholar]
  30. Keegan L., Gill G., Ptashne M. 1986; Separation of DNA binding from the transcription-activating function of a eukaryotic regulatory protein. Science 231:699–704
    [Google Scholar]
  31. Lambert P. F., Spalholz B. A., Howley P. M. 1987; A transcriptional repressor encoded by BPV-1 shares a common carboxy-terminal domain with the E2 transactivator. Cell 50:69–78
    [Google Scholar]
  32. Land H., Parada L. F., Weinberg R. A. 1983; Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature; London: 304596–602
    [Google Scholar]
  33. Luckow B., Schutz G. 1987; CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements. Nucleic Acids Research 15:5490
    [Google Scholar]
  34. Lusky M., Botchan M. R. 1984; Characterization of the bovine papillomavirus plasmid maintenance sequences. Cell 36:391–401
    [Google Scholar]
  35. Mcbride A. A., Schlegel R., Howley P. M. 1988; The carboxy-terminal domain shared by the bovine papillomavirus transactivator and repressor proteins contains a specific DNA binding activity. EMBO Journal 7:533–539
    [Google Scholar]
  36. Matlashewski G., Schneider J., Banks L., Jones N., Murray A., Crawford L. 1987; Human papillomavirus type 16 DNA cooperates with activated ras in transforming primary cells. EMBO Journal 6:1741–1746
    [Google Scholar]
  37. Pater M. M., Hughes G. A., Hyslop D. E., Nakshatri H., Pater A. 1988; Glucocorticoid-dependent oncogenic transforma-tion by type 16 but not type 11 human papillomavirus DNA. Nature; London: 335832–834
    [Google Scholar]
  38. Pettersson U., Roberts R. J. 1986; Adenovirus gene expression and replication: a historical review. Cancer Cells 4:37–52
    [Google Scholar]
  39. Phelps W. C., Yee C. L., Munger K., Howley P. M. 1988; The human papillomavirus type 16 E7 gene encodes transactivation and transformation functions similar to those of adenovirus E1A. Cell 53:539–547
    [Google Scholar]
  40. Prakash S. S., Horwitz B. H., Zibello T., Settleman J., Dimaio D. 1988; Bovine papillomavirus E2 gene regulates expression of the viral E5 transforming gene. Journal of Virology 62:3608–3613
    [Google Scholar]
  41. Rosl F., Waldeck W., Sauer G. 1983; Isolation of episomal bovine papillomavirus chromatin and identification of a DNase I hypersensitive region. Journal of Virology 46:567–574
    [Google Scholar]
  42. Rous P., Friedewald W. F. 1944; The effect of chemical carcinogens on virus-induced rabbit carcinomas. Journal of Experimental Medicine 79:511–537
    [Google Scholar]
  43. Ruley H. E. 1983; Adenovirus early region 1A enables viral and cellular transforming genes to transform primary cells in culture. Nature; London: 304602–606
    [Google Scholar]
  44. Sarver N., Rabson M. S., Yang Y. C., Byrne J. C., Howley P. M. 1984; Localization and analysis of bovine papillomavirus type 1 transforming functions. Journal of Virology 52:377–388
    [Google Scholar]
  45. Schlegel R., Phelps W. C., Zhang Y-L., Barbosa M. 1988; Quantitative keratinocyte assay detects two biological activities of human papillomavirus DNA and identifies viral types associated with cervical carcinoma. EMBO Journal 7:3181–3187
    [Google Scholar]
  46. Smits M. L., Raadsheer E., Rood I., Mehendale S., Slater R. M., Van Der Noordaa J., Ter Schegget J. 1988; Induction of anchorage-independent growth of human embryonic fibroblasts with a deletion in the short arm of chromosome 11 by human papillomavirus type 16 DNA. Journal of Virology 62:4538–4543
    [Google Scholar]
  47. Smotkin D., Wettstein F. O. 1986; Transcription of human papillomavirus type 16 early genes in a cervical cancer and a cancer-derived cell line and identification of the E7 protein. Proceedings of the National Academy of Sciences, U.S.A 83:4680–4684
    [Google Scholar]
  48. Smotkin D., Prokoph H., Wettstein F. O. 1989; Oncogenic and non-oncogenic human genital papillomaviruses generate the E7 mRNA by different mechanisms. Journal of Virology 63:1441–1447
    [Google Scholar]
  49. Southern E. M. 1975; Detection of specific sequences among DNA fragments separated by gel electrophoresis. Journal of Molecular Biology 98:503–517
    [Google Scholar]
  50. Southern P. J., 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]
  51. Spalholz B. A., Yang Y., Howley P. M. 1985; Transactivation of a bovine papillomavirus transcriptional regulatory element by the E2 gene product. Cell 42:183–191
    [Google Scholar]
  52. Spalholz B. A., Baker C. C., Lambert P. F., Howley P. M. 1987; Bovine papillomavirus type-1 E2 trans-activation: characterization of the enhancers and promoters in the long control region. Cancer Cells 5:5–13
    [Google Scholar]
  53. Stanley M. A., Brown H. M., Appleby M., Minson A. C. 1989; Properties of a non-tumorigenic human cervical keratinocyte cell line. International Journal of Cancer 43:672–676
    [Google Scholar]
  54. Storey A., Pim D., Murray A., Osborn K., Banks L., Crawford L. 1988; Comparison of the in vitro transforming activities of human papillomavirus types. EMBO Journal 7:1815–1820
    [Google Scholar]
  55. Thierry F., Yaniv M. 1987; The BPV1-E2 trans-acting protein can be either an activator or a repressor of the HPV-18 regulatory region. EMBO Journal 6:3391–3397
    [Google Scholar]
  56. Thomas P. S. 1980; Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proceedings of the National Academy of Sciences, U.S.A 77:5201–5205
    [Google Scholar]
  57. Waldeck W., Rosl R., Zentgraf H. 1984; Origin of replication in episomal bovine papillomavirus type 1 DNA isolated from transformed cells. EMBO Journal 3:2173–2178
    [Google Scholar]
  58. Wigler M., Pellicer A., Silverstein S., Axel R., Urlaub G., Chasin L. 1979; DNA-mediated transfer of the adenine phosphoribosyltransferase locus into mammalian cells. Proceedings of the National Academy of Sciences, U.S.A 76:1373–1376
    [Google Scholar]
  59. Young L. S., Bevan I. S., Johnson M. A., Blomfield P. I., Brombridge T., Maitland N. J., Woodman C. B. J. 1989; The polymerase chain reaction: a new epidemiological tool for investigating cervical human papillomavirus infection. British Medical Journal 298:14–18
    [Google Scholar]
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