First Author | Martín-Oliva D | Year | 2004 |
Journal | Oncogene | Volume | 23 |
Issue | 31 | Pages | 5275-83 |
PubMed ID | 15077172 | Mgi Jnum | J:91204 |
Mgi Id | MGI:3046120 | Doi | 10.1038/sj.onc.1207696 |
Citation | Martin-Oliva D, et al. (2004) Crosstalk between PARP-1 and NF-kappaB modulates the promotion of skin neoplasia. Oncogene 23(31):5275-83 |
abstractText | 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-kappaB, 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-kappaB is a hallmark for tumorigenesis together with the concomitant release of early inflammatory mediators. In the absence of PARP-1, NF-kappaB activation and induction kappaB-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-kappaB and might have an important implication in targeting PARP-1 as a new antineoplastic therapeutic approach. |