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  • Original Paper
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Wild-type p53 gene transfer is not detrimental to normal cells in vivo: implications for tumor gene therapy

Oncogene volume 23, pages 418–425 (2004)Cite this article

Abstract

The p53 oncosuppressor is strictly maintained in an inactive form under normal conditions, while it is post-translationally activated by a variety of stresses, enacting different protective biological functions. Since one critical issue in cancer gene therapy is tumor specificity, we asked whether the tight p53 regulation applies also to exogenously transferred p53. In principle, this type of regulation could allow p53 gene transfer in both normal and tumor cells to produce detrimental effects only in the latter ones. Here, we report that primary bone marrow cells infected with a p53 recombinant retrovirus and transplanted into irradiated mice reconstitute the hematopoietic system, with no detectable alterations in any of its compartments. Furthermore, simultaneous infection of leukemia and bone marrow cells depleted the neoplastic contamination, allowing lifelong, disease-free survival of 65% of the transplanted animals. These results show that exogenous p53 is controlled as tightly as the endogenous one, and opens the way to p53 gene therapy, without requiring tumor targeting.

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Acknowledgements

We gratefully acknowledge Ian Pragnell for helpful advice on BM culturing, Gary Nolan for the gift of packaging cells, the Radiation Therapy Department of the Regina Elena Cancer Institute, Marco Scarsella, and Enrico Spugnini for their assistance in the mice irradiation and BM transplantation, and Silvia Bacchetti for critical revision of the manuscript. This work was supported by grants from Associazione Italiana per la Ricerca sul Cancro (AIRC), Italia–USA project, and Ministero della Salute. GB and AP were recipients of fellowships from the Fondazione Italiana per la Ricerca sul Cancro (FIRC).

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  1. Contributed equally to this work

Authors and Affiliations

  1. Department of Experimental Oncology, Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, Via delle Messi d'Oro 156, Rome, 00158, Italy

    Gianluca Bossi, Giuseppina Mazzaro, Alessandro Porrello, Silvia Soddu & Ada Sacchi

  2. Laboratory of Comparative Toxicology and Ecotoxicology, Istituto Superiore di Sanita', Viale Regina Elena 299, Rome, 00161, Italy

    Marco Crescenzi

Authors
  1. Gianluca Bossi
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  2. Giuseppina Mazzaro
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  3. Alessandro Porrello
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  4. Marco Crescenzi
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  5. Silvia Soddu
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  6. Ada Sacchi
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Correspondence to Silvia Soddu or Ada Sacchi.

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Bossi, G., Mazzaro, G., Porrello, A. et al. Wild-type p53 gene transfer is not detrimental to normal cells in vivo: implications for tumor gene therapy. Oncogene 23, 418–425 (2004). https://doi.org/10.1038/sj.onc.1207042

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