1887

Abstract

Bovine papillomavirus type 4 (BPV-4) does not possess an E6 ORF. The E6 oncoprotein of human papillomavirus (HPV) binds and degrades the tumour suppressor protein p53, thus contributing to tumour progression. Since BPV-4 lacks E6, it is unknown how the virus evades the tumour suppressor properties of p53 in the induction of tumours of the gastrointestinal tract. Mutations in the p53 gene have been detected both in papillomas and carcinomas, suggesting that p53 dysfunction plays a part in these neoplasias. BPV-4 can transform primary foetal bovine cells (PalFs) in cooperation with an activated gene, but the transformed cells are neither immortal nor tumori- genic. Co-transfection with the HPV-16 E6 (16E6) ORF confers immortality but not tumorigenicity. To investigate the role of p53 in BPV-4 cell transformation , we transfected PalFs and p53- null mouse fibroblasts with BPV-4 DNAin combinations with , 16E6 ORF and mutant (V143A) p53 cDNA. Transfection of PalFs with BPV-4 DNA, and mutant p53 led to cell immortalization, indicating that 16E6 and mutant p53 are functionally equivalent in conferring immortality. However, cotransfection of PalFs with BPV-4 DNA, , and both mutant p53 cDNA and 16E6 ORF resulted in cells which were fully transformed to tumorigenicity. In p53-null mouse fibroblasts, BPV-4 DNA induced transformation by itself, but the transformed cells were incapable of suspension growth. The cotransfection of BPV-4 DNA with 16E6ORF produced many more transformed colonies and the cells were capable of growing in suspension. In this system, therefore, 16E6 confers anchorage-independence to BPV-4-transformed cells in a p53-independent fashion.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-78-11-3001
1997-11-01
2022-08-15
Loading full text...

Full text loading...

/deliver/fulltext/jgv/78/11/9367387.html?itemId=/content/journal/jgv/10.1099/0022-1317-78-11-3001&mimeType=html&fmt=ahah

References

  1. Anderson R. A., Scobie L., O’Neil B. W., Grindlay G. J., Campo M. S. 1997; Viral proteins of bovine papillomavirus type 4 during the development of alimentary canal tumours. The Veterinary Journal 154:69–78
    [Google Scholar]
  2. Avila M. A., Velasco J. A., Cansado J., Notario V. 1994; Quercetin mediates the down-regulation of mutant p53 in the human breast cancer cell line MDA-MB468. Cancer Research 54:2424–2428
    [Google Scholar]
  3. Baker S. J., Markowitz S., Fearon E. R., Willson J. K. V., Vogelstein B. 1990; Suppression of human colorectal carcinoma cell growth by wild-type p53. Science 249:912–915
    [Google Scholar]
  4. Barbosa M. S., Lowy D. R., Schiller J. T. 1989; Papillomavirus polypeptides E6 and E7 are zinc-binding proteins. Journal of Virology 63:1404–1407
    [Google Scholar]
  5. Cairney M., Campo M. S. 1995; The synergism between bovine papillomavirus type 4 and quercetin is dependent on the timing of exposure. Carcinogenesis 16:1997–2001
    [Google Scholar]
  6. Campo M. S., Jarrett W. F. H. 1987; Papillomavirus and disease. In Molecular Basis of Virus Disease, SGM symposium 40 pp. 215–243 Russel W. C., Almond J. W. Edited by Reading, UK: Society for General Microbiology;
    [Google Scholar]
  7. Campo M. S., Spandidos D. A. 1983; Molecularly cloned bovine papillomavirus DNA transforms mouse fibroblasts in vitro. Journal of General Virology 64:549–557
    [Google Scholar]
  8. Campo M. S., Moar M. H., Sartirana M. L., Kennedy I. M., Jarrett W. F. H. 1985; The presence of bovine papillomavirus type 4 DNA is not required for the progression to and the maintenance of the malignant state in cancers of the alimentary canal in cattle. EMBO Journal 4:1819–1825
    [Google Scholar]
  9. Campo M. S., McCaffery R. E., Doherty I., Kennedy I. M., Jarrett W. F. H. 1990; The Harvey ras 1 gene is activated in papillomavirus- associated carcinomas of the upper alimentary canal in cattle. Oncogene 5:303–308
    [Google Scholar]
  10. Campo M. S., O’Neil B. W., Barron R. J., Jarrett W. F. H. 1994; Experimental reproduction of the papilloma-carcinoma complex of the alimentary canal in cattle. Carcinogenesis 15:1597–1601
    [Google Scholar]
  11. Chandrachud L. M., O’Neil B. W., Jarrett W. F. H., Grindlay G. J., McGarvie G. M., Campo M. S. 1994; Humoral immune response to the E7 protein of bovine papillomavirus type 4 and identification of B-cell epitopes. Virology 200:98–104
    [Google Scholar]
  12. Choo K.-B., Chong K. Y. 1993; Absence of mutation in the p53 and retinoblastoma susceptibility genes in primary cervical carcinomas. Virology 193:1042–1046
    [Google Scholar]
  13. Coggins L. W., Scobie L., Jackson M. E., Campo M. S. 1995; Assignment of the bovine p53 gene to chromosome 19q15 by fluorescence in situ hybridization. Mammalian Genome 6:687–688
    [Google Scholar]
  14. Crook T., Tidy J. A., Vousden K. H. 1991a; Degradation ofp53 can be targeted by HPV E6 sequences distinct from those required for p53 binding and trans-activation. Cell 67:547–556
    [Google Scholar]
  15. Crook T., Wrede D., Vousden K. H. 1991b; p53 point mutation in HPV negative human cervical carcinoma cell lines. Oncogene 6:873–875
    [Google Scholar]
  16. Donehower L. A., Harvey M., Slagle B. L., McArthur M. J., Montgomery C. A., Butel J. S., Bradley A. T. 1992; Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 356:215–221
    [Google Scholar]
  17. Faccini A. M., Cairney M., Ashrafi G. H., Finbow M. E., Campo M. S., Pitts J. D. 1996; The bovine papillomavirus type 4 E8 protein binds to ductin and causes loss of gap junctional intercellular communication in primary fibroblasts. Journal of Virology 70:9041–9045
    [Google Scholar]
  18. Fujita M., Inoue M., Tanizawa O., Iwamoto S., Enomoto T. 1992; Alterations of the p53 gene in human primary cervical carcinoma with and without human papillomavirus infection. Cancer Research 52:5323–5328
    [Google Scholar]
  19. Gaukroger J., Chandrachud L., Jarrett W. F. H., McGarvie G. E., Yeudall W. A., McCaffery R. E., Smith K. T., Campo M. S. 1991; Malignant transformation of a papilloma induced by bovine papillomavirus type 4 in the nude mouse renal capsule. Journal of General Virology 72:1165–1168
    [Google Scholar]
  20. Giri I., Danos O. 1986; Papillomavirus genomes: from sequence data to biological properties. Trends in Genetics 2:227–232
    [Google Scholar]
  21. Harvey M., Sands A. T., Weiss R. S., Hegi M. E., Wiseman R. W., Pantazis P., Giovanella B. C., Tainsky M. A., Bradley A., Donehower L. A. 1993; In vitro growth characteristics of embryo fibroblasts isolated from p53-deficient mice. Oncogene 8:2457–2467
    [Google Scholar]
  22. Jackson M. E., Pennie W. D., McCaffery R. E., Smith K. T., Grindlay G. J., Campo M. S. 1991; The B subgroup bovine papillomaviruses lacks an identifiable E6 open reading frame. Molecular Carcinogenesis 4:382–387
    [Google Scholar]
  23. Jaggar R. T., Pennie W. D., Smith K. T., Jackson M. E., Campo M. S. 1990; Cooperation between bovine papillomavirus type 4 and ras in the morphological transformation of primary bovine fibroblasts. Journal of General Virology 71:3041–3046
    [Google Scholar]
  24. Munger K., Werness B. A., Dyson N., Phelps W. C., Harlow E., Howley P. M. 1989; Compl ex formation of human papillomavirus E7 proteins with the retinoblastoma tumour suppressor gene product. EMBO Journal 8:4099–4105
    [Google Scholar]
  25. Munger K., Scheffner M., Huibregtse J. M., Howley P. M. 1992; Interactions of HPV E6 and E7 oncoproteins with tumour suppressor gene products. Cancer Surveys 12:197–217
    [Google Scholar]
  26. Pennie W. D., Campo M. S. 1992; Synergism between bovine papillomavirus type 4 and the flavonoid quercetin in cell transformation in vitro. Virology 190:861–865
    [Google Scholar]
  27. Pennie W. D., Grindlay G. J., Cairney M., Campo M. S. 1993; Analysis of the transforming functions of bovine papillomavirus type 4. Virology 193:614–620
    [Google Scholar]
  28. Plaumann B., Fritsche M., Rimpler H., Brandner G., Hess R. D. 1996; Flavonoids activate wild-type 53. Oncogene 13:1605–1614
    [Google Scholar]
  29. Scheffner M., Werness B. A., Huibregtse J. M., Levine A. J., Howley P. M. 1990; The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63:1129–1136
    [Google Scholar]
  30. Scobie L. 1996 The role of p53 in cell transformation by BPV-4 PhD thesis University of Glasgow, UK:
    [Google Scholar]
  31. Sedman S. A., Hubbert N. L., Vass W. C., Lowy D. R., Schiller J. T. 1992; Mutant p53 can substitute for human papillomavirus type 16 E6 in immortalisation of human keratinocytes but does not have E6 associated transactivation or transforming activity. Journal of Virology 66:4201–4208
    [Google Scholar]
  32. Smith K. T., Campo M. S. 1988; ‘Hit and run’ transformation of mouse C127 cells by bovine papillomavirus type 4: the viral DNA is required for the initiation but not for maintenance of the transformed phenotype. Virology 164:39–47
    [Google Scholar]
  33. 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]
  34. Zatsepina O., Braspenning J., Robberson D., Hajibagheri M. A. N., Blight K. J., Ely S., Hibma M., Spitkovsky D., Trendelenburg M., Crawford L., Tommasino M. 1997; The human papillomavirus type 16 E7 protein is associated with the nucleolus in mammalian and yeast cells. Oncogene 14:1137–1145
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-78-11-3001
Loading
/content/journal/jgv/10.1099/0022-1317-78-11-3001
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error