Studies regarding the functions of the bovine papillomavirus (BPV) E7 oncoprotein are lacking and no E7-mediated mechanism underlying mesenchymal carcinogenesis is known. Here, we show that the interaction between the 600 kDa retinoblastoma protein-associated factor (p600) and BPV E7, described in cultured cells, takes place in naturally occurring equine sarcoids. In these cancers we detect the expression of E7 and p600, and demonstrate that E7 and p600 co-localize and physically interact. Furthermore, intracellular signals involved in p600 functional activity are found not to be overexpressed, suggesting a different functional activity of p600 in naturally occurring carcinogenesis. Our results demonstrate, for the first time, that E7–p600 interaction occurs during the natural history of BPV-induced equine tumours, suggesting an important role for E7 in carcinogenesis. Finally, the system provides a suitable animal model of papillomavirus-associated cancer to test therapeutic vaccination against E7.


Article metrics loading...

Loading full text...

Full text loading...



  1. Bohl, J., Hull, B. & Vande Pol, S. B.(2001). Cooperative transformation and coexpression of bovine papillomavirus type 1 E5 and E7 protein. J Virol 75, 513–521.[CrossRef] [Google Scholar]
  2. Borzacchiello, G. & Roperto, F.(2008). Bovine papillomaviruses, papillomas and cancer in cattle. Vet Res 39, 45–63.[CrossRef] [Google Scholar]
  3. Borzacchiello, G., Russo, V., Spoleto, C., Roperto, S., Balcos, L., Rizzo, C., Venuti, A. & Roperto, F.(2007). Bovine papillomavirus type-2 DNA and expression of E5 and E7 oncoproteins in vascular tumours of the urinary bladder in cattle. Cancer Lett 250, 82–91.[CrossRef] [Google Scholar]
  4. Borzacchiello, G., Russo, V., Della Salda, L., Roperto, S. & Roperto, F.(2008). Platelet derived growth factor β receptor and bovine papillomavirus E5 and E7 oncoproteins expression in equine sarcoids. J Comp Pathol 139, 231–237.[CrossRef] [Google Scholar]
  5. Brandt, S., Tober, R., Walter, L., Klein, D. & Steinborn, R.(2010). BPV-1 infection in horses also involves the epidermis. In Proceedings of the 1st International Workshop on Papillomavirus E5 Oncogene, p. 19. Edited by G. Borzacchiello. Capri, Italy: Federiciana Editrice.
  6. Campo, M. S.(2003). Papillomavirus and disease in humans and animals. Vet Comp Oncol 1, 3–14.[CrossRef] [Google Scholar]
  7. Chambers, G., Ellsmore, V. A., O'Brien, P. M., Reid, S. W. J., Love, S., Campo, M. S. & Nasir, L.(2003). Association of bovine papillomavirus with the equine sarcoid. J Gen Virol 84, 1055–1062.[CrossRef] [Google Scholar]
  8. DeMasi, J., Huh, K. W., Nakatani, Y., Münger, K. & Howley, P. M.(2005). Bovine papillomavirus E7 transformation function correlates with cellular p600 protein binding. Proc Natl Acad Sci U S A 102, 11486–11491.[CrossRef] [Google Scholar]
  9. DeMasi, J., Chao, M. C., Kumar, A. S. & Howley, P. M.(2007). Bovine papillomavirus E7 oncoprotein inhibits anoikis. J Virol 81, 9419–9425.[CrossRef] [Google Scholar]
  10. Dvoretzky, I., Shober, R. & Lowy, D.(1980). Focus assay in mouse cells for bovine papillomavirus. Virology 103, 369–375.[CrossRef] [Google Scholar]
  11. Huh, K. W., DeMasi, J., Ogawa, H., Nakatani, Y., Howley, P. M. & Munger, K.(2005). Association of the human papillomavirus type 16 E7 oncoprotein with the 600-kDa retinoblastoma protein-associated factor, p600. Proc Natl Acad Sci U S A 102, 11492–11497.[CrossRef] [Google Scholar]
  12. Hungerford, J. E., Compton, M. T., Matter, M. L., Hoffstrom, B. G. & Otey, C. A.(1996). Inhibition of pp125FAK in cultured fibroblasts results in apoptosis. J Cell Biol 135, 1383–1390.[CrossRef] [Google Scholar]
  13. Marti, E., Lazary, S., Antczak, D.F. & Gerber, H. ((1993). Report of the first international workshop on equine sarcoid. Equine Vet J 25, 397–407.[CrossRef] [Google Scholar]
  14. Münger, K., Werness, B. A., Dyson, N., Phelps, W. C. & Howley, P. M.(1989). Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product. EMBO J 8, 4099–4105. [Google Scholar]
  15. Nakatani, Y., Konishi, H., Vassilev, A., Kurooka, H., Ishiguro, K., Sawada, J., Ikura, T., Korsmeyer, S. J., Qin, J. & other authors(2005). p600, a unique protein required for membrane morphogenesis and cell survival. Proc Natl Acad Sci U S A 102, 15093–15098.[CrossRef] [Google Scholar]
  16. Nasir, L. & Campo, M. S.(2008). Bovine papillomaviruses: their role in the aetiology of cutaneous tumours of bovids and equids. Vet Dermatol 19, 243–254.[CrossRef] [Google Scholar]
  17. Nasir, L. & Reid, S. W. J.(2006). BPV in equine sarcoids. In Papillomavirus Research: from Natural History to Vaccines and Beyond, pp. 289–420. Edited by Campo, M. S.. Norfolk, UK. : Caister Academic Press. [Google Scholar]
  18. Owens, L. V., Xu, L., Craven, R. J., Dent, G. A., Weiner, T. M., Kornberg, L., Liu, E. T. & Cance, W. G.(1995). Overexpression of the focal adhesion kinase (p125FAK) in invasive human tumors. Cancer Res 55, 2752–2755. [Google Scholar]
  19. 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. J Virol 52, 377–388. [Google Scholar]
  20. van Nimwegen, M. J. & van de Water, B.(2007). Focal adhesion kinase: a potential target in cancer therapy. Biochem Pharmacol 73, 597–609.[CrossRef] [Google Scholar]

Data & Media loading...

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