Inhibition of Sp1 activity by a decoy PNA-DNA chimera prevents urokinase receptor expression and migration of breast cancer cells (Articolo in rivista)

Type
Label
  • Inhibition of Sp1 activity by a decoy PNA-DNA chimera prevents urokinase receptor expression and migration of breast cancer cells (Articolo in rivista) (literal)
Anno
  • 2005-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1016/j.bcp.2005.07.024 (literal)
Alternative label
  • Zannetti A, Del Vecchio S, Romanelli A, Scala S, Saviano M, Cali' G, Stoppelli MP, Pedone C, Salvatore M (2005)
    Inhibition of Sp1 activity by a decoy PNA-DNA chimera prevents urokinase receptor expression and migration of breast cancer cells
    in Biochemical pharmacology
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Zannetti A, Del Vecchio S, Romanelli A, Scala S, Saviano M, Cali' G, Stoppelli MP, Pedone C, Salvatore M (literal)
Pagina inizio
  • 1277 (literal)
Pagina fine
  • 1287 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 70 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#note
  • Articolo scientifico (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#descrizioneSinteticaDelProdotto
  • Articolo scientifico (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Istituto di Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerche, Via S. Pansini 5, 80131 Naples, Italy Istituto di Endocrinologia ed Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, Naples, Italy Istituto Internazionale di Genetica e Biofisica, Consiglio Nazionale delle Ricerche, Naples, Italy Dipartimento di Scienze Biomorfologiche e Funzionali, Universita' ''Federico II'', Naples, Italy (literal)
Titolo
  • Inhibition of Sp1 activity by a decoy PNA-DNA chimera prevents urokinase receptor expression and migration of breast cancer cells (literal)
Abstract
  • Sp1 regulates the activation of many genes involved in tumor growth, apoptosis, and angiogenesis. We have previously shown the involvement of Sp1 in the up-regulation of urokinase receptor (uPAR) expression, a key mol. in tumor invasion and metastasis. Here, we investigated whether a marked down-regulation of Sp1 activity may inhibit uPAR expression and migration ability of MDA-MB-231 breast cancer cells. To this end, we tested the decoy ability of a novel peptide nucleic acid (PNA)-DNA chimera which carries a central DNA strand, contg. Sp1-binding sequence, covalently linked to two PNA fragments at both ends (PNA-DNA-PNA, PDP). The chimera was synthesized, annealed with complementary DNA (PDP-DNA), and then tested for its ability to bind Sp1 both in vitro and in living MDA-MB-231 breast cancer cells in the presence of urokinase (uPA). This PDP-DNA decoy mol. efficiently competes for the binding to endogenous Sp1 in nuclear exts., and upon transfection with liposomal vectors, causes a marked decrease of available Sp1 in both untreated and uPA-treated MDA-MB-231 cells. Accordingly, both uPA-dependent enhancement of uPAR expression and cell migration were strongly reduced in transfected cells. Interestingly, a detectable inhibitory effect is also obsd. in breast cancer cells exposed to PDP-DNA in the absence of transfection reagents. Finally, the inhibitory effect of PDP-DNA appeared to be stronger than that obsd. with oligonucleotides carrying Sp1 consensus sequence. Our findings show that this novel PNA-DNA chimera, contg. Sp1 consensus sequence, effectively inhibits Sp1 activity, uPAR expression, and motility of breast cancer cells indicating its potential therapeutic use to prevent tumor dissemination. (literal)
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