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Anticancer activity of an adenoviral vector expressing short hairpin RNA against BK virus T-ag

Cancer Gene Therapy volume 14, pages 297–305 (2007)Cite this article

Abstract

The human polyomavirus BK (BKV) is oncogenic in rodents and induces malignant transformation of rodent cells in vitro. Although its role in human tumorigenesis is still debated, BKV represents an excellent model to evaluate molecularly targeted antineoplastic approaches. Here, we have tested whether stable suppression of the T antigen (T-ag) oncogene expression could inhibit the in vitro and in vivo malignant phenotype of BKV-transformed mouse cells. An adenovirus vector system that expresses small hairpin RNAs (shRNAs), which are converted into active small interfering RNAs (siRNA) molecules against the BKV T-ag, was developed. This vector was able to inhibit the expression of BKV T-ag through a highly efficient in vitro and in vivo delivery of the siRNA molecule. In addition, it allowed a stable expression of siRNA for a period of time sufficient to elicit a biological effect. Inhibition of T-ag expression results in reduction of the in vitro growth rate of BKV-transformed cells, which is, at least in part, caused by restoration of p53 activity and induction of apoptosis. In vivo studies proved that adenovirus vectors expressing anti-T-ag siRNA were able to suppress tumorigenicity of BKV-transformed cells. Moreover, adenovirus vector direct treatment of growing tumors resulted in a significant reduction of tumor growth. This study indicates that siRNAs delivery via a viral vector have a potential usefulness as i n vivo anticancer tool against viral and cellular oncogenes.

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Acknowledgements

We thank Professor Giuseppe Barbanti-Brodano for critical review of the paper. We thank Augusto Bevilacqua, Pietro Zucchini, Annalisa Peverati and Iva Pivanti for the excellent technical support. This work was supported by grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC) and by the Italian Ministero dell’Istruzione, Università e Ricerca scientifica (MIUR) and by Comitato dei Sostenitori – Progetto CAN2006.

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Authors and Affiliations

  1. Dipartimento di Medicina Sperimentale e diagnostica e Centro Interdipartimentale per la Ricerca sul Cancro, Università di Ferrara, Ferrara, Italy

    S Sabbioni, E Callegari, R Spizzo, A Veronese, A Corallini & M Negrini

  2. Istituto di Anatomia ed Istologia Patologica, Università di Padova, Padova, Italy

    G Altavilla

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  1. S Sabbioni
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  2. E Callegari
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  5. G Altavilla
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  6. A Corallini
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  7. M Negrini
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Correspondence to M Negrini.

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Sabbioni, S., Callegari, E., Spizzo, R. et al. Anticancer activity of an adenoviral vector expressing short hairpin RNA against BK virus T-ag. Cancer Gene Ther 14, 297–305 (2007). https://doi.org/10.1038/sj.cgt.7701014

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