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Adenovirus-mediated TA-p73β gene transfer increases chemosensitivity of human malignant melanomas

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Abstract

Malignant melanoma is the most aggressive form of skin cancer and has proven to be highly resistant to conventional chemotherapy. Intriguingly, the p53 tumor suppressor, a main mediator of chemoresistance in other tumor types, is rarely mutated in melanoma. However, we have previously shown that anti-apoptotic isoforms of p73 (ΔTA-p73), another member of the p53 family, are overexpressed in metastatic melanomas. ΔTA-p73 can oppose the pro-apoptotic functions of p53 and full length p73, and thus it could contribute to melanoma chemoresistance. In this study, we use an efficient adenoviral-based gene transfer approach to introduce a transcriptionally active form of p73 (TA-p73β) in melanoma cells, with the objective of overcoming drug resistance. Interestingly, TA-p73β significantly sensitized 5 out of 7 aggressive melanoma cell lines to the standard therapeutic agents adriamycin and cisplatin. More importantly, TA-p73β displayed a synergistic effect in vivo allowing adriamycin or cisplatin to block melanoma cell growth in mouse xenograft models (p < 0.05). In summary, our data show that Ad-mediated TA-p73β gene expression can markedly sensitize a subset of melanoma cell lines to adriamycin and cisplatin in vitro and in vivo, suggesting a new chemosensitization strategy for malignant melanomas.

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Authors and Affiliations

  1. Department of Vectorology and Experimental Gene Therapy, University of Rostock, Schillingallee 70, Rostock, 18055, Germany

    S. Tuve, T. Racek, A. Niemetz, J. Schultz & B. M. Pützer

  2. Department of Dermatology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, 28109, USA

    M. S. Soengas

  3. Department of Vectorology and Experimental Gene Therapy, University of Rostock, Schillingallee 70, Rostock, D-18055, Germany

    B. M. Pützer

Authors
  1. S. Tuve
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  2. T. Racek
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  3. A. Niemetz
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  4. J. Schultz
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  5. M. S. Soengas
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  6. B. M. Pützer
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Correspondence to B. M. Pützer.

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Tuve, S., Racek, T., Niemetz, A. et al. Adenovirus-mediated TA-p73β gene transfer increases chemosensitivity of human malignant melanomas. Apoptosis 11, 235–243 (2006). https://doi.org/10.1007/s10495-006-3407-0

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  • DOI: https://doi.org/10.1007/s10495-006-3407-0

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