Raised expression of the antiapoptotic protein ped/pea-15 increases susceptibility to chemically induced skin tumor development. (Articolo in rivista)

Type
Label
  • Raised expression of the antiapoptotic protein ped/pea-15 increases susceptibility to chemically induced skin tumor development. (Articolo in rivista) (literal)
Anno
  • 2005-01-01T00:00:00+01:00 (literal)
Alternative label
  • Formisano P; Perruolo G; Libertini S; Santopietro S; Troncone G; Raciti GA; Oriente F; Portella G; Miele C; Beguinot F. (2005)
    Raised expression of the antiapoptotic protein ped/pea-15 increases susceptibility to chemically induced skin tumor development.
    in Oncogene (Basingstoke)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Formisano P; Perruolo G; Libertini S; Santopietro S; Troncone G; Raciti GA; Oriente F; Portella G; Miele C; Beguinot F. (literal)
Pagina inizio
  • 7012 (literal)
Pagina fine
  • 7021 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 24 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Dipartimento di Biologia e Patologia Cellulare e Molecolare, Universita` di Napoli Federico II, Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Via Sergio Pansini, 5, Naples 80131, Italy; Dipartimento di Scienze Biomorfologiche e Funzionali of the Federico II University of Naples, Naples, Italy (literal)
Titolo
  • Raised expression of the antiapoptotic protein ped/pea-15 increases susceptibility to chemically induced skin tumor development. (literal)
Abstract
  • ped/pea-15 is a cytosolic protein performing a broad antiapoptotic function. We show that, upon DMBA/TPA-induced skin carcinogenesis, transgenic mice overexpressing ped/pea-15 (Tg(ped/pea-15)) display early development of papillomas and a four-fold increase in papilloma number compared to the nontransgenic littermates (P < 0.001). The malignant conversion frequency was 24% for the Tg(ped/pea-15) mice and only 5% in controls (P < 0.01). The isolated application of TPA, but not that of DMBA, was sufficient to reversibly upregulate ped/pea-15 in both untransformed skin and cultured keratinocytes. ped/pea15 protein levels were also increased in DMBA/TPA-induced papillomas of both Tg(ped/pea-15) and control mice. Isolated TPA applications induced Caspase-3 activation and apoptosis in nontransformed mouse epidermal tissues. The induction of both Caspase-3 and apoptosis by TPA were four-fold inhibited in the skin of the Tg(ped/pea-15) compared to the nontransgenic mice, accompanied by a similarly sized reduction in TPA-induced JNK and p38 stimulation and by constitutive induction of cytoplasmic ERK activity in the transgenics. ped/pea-15 expression was stably increased in cell lines from DMBA/TPA-induced skin papillomas and carcinomas, paralleled by protection from TPA apoptosis. In the A5 spindle carcinoma cell line, antisense inhibition of ped/pea-15 expression simultaneously rescued sensitivity to TPA-induced Caspase-3 function and apoptosis. The antisense also reduced A5 cell ability to grow in semisolid media by 65% (P < 0.001) and increased by three-fold tumor latency time (P < 0.01). Thus, the expression levels of ped/pea-15 control Caspase-3 function and epidermal cell apoptosis in vivo and determine susceptibility to skin tumor development. (literal)
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