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  • Original Article
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Bovine papillomavirus E5 oncoprotein binds to the activated form of the platelet-derived growth factor β receptor in naturally occurring bovine urinary bladder tumours

Oncogene volume 25, pages 1251–1260 (2006)Cite this article

Abstract

Studies regarding the functions of the bovine papillomavirus (BPV) E5 oncoprotein in vivo are lacking and no E5-mediated mechanism underlying epithelial carcinogenesis is known. We have shown that BPV-2 DNA is present in the majority of naturally occurring urinary bladder tumours of cattle and that E5 is expressed in the cancer cells. Here we show that the interaction between the platelet-derived growth factor (PDGF) β receptor and BPV E5, described in vitro in cultured cells, takes place in vivo in bovine urinary bladder cancers. In these cancers, E5 and PDGF β receptor colocalize, as shown by confocal microscopy, and physically interact, as shown by coimmunoprecipitation. Furthermore, the PDGF β receptor associated with E5 is highly phosphorylated, suggesting the functional activation of the receptor upon E5 interaction. Our results demonstrate, for the first time, that E5–PDGF β receptor interaction occurs during the natural history of bovine urinary bladder tumours, suggesting an important role for E5 in carcinogenesis. Finally, the system provides a suitable animal model of papillomavirus-associated cancer to test therapeutic vaccination against E5. Successful bladder tumour regression would provide a valuable model for therapeutic vaccination against papillomavirus-associated tumours.

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Acknowledgements

We are indebted to Professor Daniel DiMaio for his kind gift of the anti-PDGF β receptor antibody and for his critical comments on this work. We are grateful also to Professors Richard Schlegel and Tung-Tien Sun for their kind gifts of anti-E5 antibody and anti-uroplakin III antibody, respectively. This work was supported in part by the Ministero dell'Istruzione, Università e Ricerca (MIUR) – PRIN; Progetto legge regionale no. 5 (2004) – Regione Campania; Ministry of Health and Compagnia San Paolo, Turin. MSC is a Fellow of Cancer Research UK.

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Authors and Affiliations

  1. Department of Pathology and Animal health, Faculty of Veterinary Medicine, Naples University ‘Federico II’, Naples, Italy

    G Borzacchiello, V Russo, F Roperto & S Roperto

  2. Department of Cellular and Molecular Biology and Pathology ‘L.Califano’ c/o Istituto di Endocrinologia e Oncologia Sperimentale IEOS CNR, Naples, Italy

    F Gentile & L Nitsch

  3. Regina Elena Cancer Institute, Laboratory of Virology, Rome, Italy

    A Venuti

  4. Division of Pathological Sciences, Institute of Comparative Medicine, University of Glasgow, Glasgow, UK

    M S Campo

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  1. G Borzacchiello
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  2. V Russo
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  3. F Gentile
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  4. F Roperto
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  5. A Venuti
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  6. L Nitsch
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  7. M S Campo
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  8. S Roperto
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Correspondence to G Borzacchiello.

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Borzacchiello, G., Russo, V., Gentile, F. et al. Bovine papillomavirus E5 oncoprotein binds to the activated form of the platelet-derived growth factor β receptor in naturally occurring bovine urinary bladder tumours. Oncogene 25, 1251–1260 (2006). https://doi.org/10.1038/sj.onc.1209152

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