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  • Original Paper
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Crosstalk between PARP-1 and NF-κB modulates the promotion of skin neoplasia

Oncogene volume 23, pages 5275–5283 (2004)Cite this article

Abstract

Poly (ADP-ribose) polymerase-1 (PARP-1)-deficient mice are protected against septic shock, type I diabetes, stroke and inflammation. It is now accepted that inflammation and related events, such as activation of NF-κB, are key components in the initiation and progression of epithelial cancer and in particular in the neoplastic transformation of keratinocytes and skin carcinogenesis. Here, we report that PARP-1-deficient mice display a strikingly reduced susceptibility to skin carcinogenesis. In parp-1−/− mice, development of papilloma-like premalignant lesions induced with DMBA and TPA, is strongly delayed and the final number of tumor-bearing mice and total tumor number were significantly reduced. In addition, epidermis of parp-1−/− mice did not show increased proliferation rates after treatment with carcinogen. Deregulated NF-κB is a hallmark for tumorigenesis together with the concomitant release of early inflammatory mediators. In the absence of PARP-1, NF-κB activation and induction κB-target genes did not take place during the promotion of tumor development. These results suggest that PARP-1 abolition impairs the promotion of skin carcinogenesis interfering with the activation of NF-κB and might have an important implication in targeting PARP-1 as a new antineoplastic therapeutic approach.

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Acknowledgements

We would like to acknowledge very specially to the officials of the animal facility at the IPBLN, CSIC, Dolores Beriso García and Francisco Ferrer Gamarra. This work has been funded by Fondo de Investigaciones Sanitarias (Grants 00/0941 and G03/15 to FJO and Grant PI021505 and HF 2001-0067 to RGM), and Spanish Ministry for Science and Technology (Grant SAF2001-3533) to JMRA, DMO, JAMG and MTV were supported by Fellowships from Fondo de Investigaciones Sanitarias.

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Authors and Affiliations

  1. University Hospital, San Cecilio, Granada

    David Martín-Oliva, Jose A Muñoz-Gámez & M Teresa Valenzuela

  2. Department of Pathology, University of Granada,

    Francisco O'Valle, Mariano Aguilar & Raimundo Garcia del Moral

  3. Department of Radiology and Physical Medicine, University of Granada,

    M Isabel Nuñez & JM Ruiz de Almodóvar

  4. Institute of Parasitology and Biomedicine, CSIC, Granada, Spain

    F Javier Oliver

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  1. David Martín-Oliva
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Correspondence to F Javier Oliver.

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Martín-Oliva, D., O'Valle, F., Muñoz-Gámez, J. et al. Crosstalk between PARP-1 and NF-κB modulates the promotion of skin neoplasia. Oncogene 23, 5275–5283 (2004). https://doi.org/10.1038/sj.onc.1207696

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