The sensitivity of MCF10A breast epithelial cells to alkylating drugs is enhanced by the inhibition of O-6 methylguanine-DNA methyltransferase transcription with a synthetic double strand DNA oligonucleotide (Articolo in rivista)

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  • The sensitivity of MCF10A breast epithelial cells to alkylating drugs is enhanced by the inhibition of O-6 methylguanine-DNA methyltransferase transcription with a synthetic double strand DNA oligonucleotide (Articolo in rivista) (literal)
Anno
  • 2002-01-01T00:00:00+01:00 (literal)
Alternative label
  • Mariani L., Piccirilli A., Citti L., Colombo M.G., Poliseno L., Rainaldi G. (2002)
    The sensitivity of MCF10A breast epithelial cells to alkylating drugs is enhanced by the inhibition of O-6 methylguanine-DNA methyltransferase transcription with a synthetic double strand DNA oligonucleotide
    in Breast cancer research and treatment (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Mariani L., Piccirilli A., Citti L., Colombo M.G., Poliseno L., Rainaldi G. (literal)
Pagina inizio
  • 1 (literal)
Pagina fine
  • 7 (literal)
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  • Prodotto di specifico interesse in una rivista del settore con “impact factor” di 3,132 (anno 2002). (literal)
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  • 2058 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#descrizioneSinteticaDelProdotto
  • Modello di inibizione di una funzione genica mediante la somministrazione di un oligonucleotide sintetico in grado di complessare l’attivatore trascrizionale del gene. (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Mariani L., Piccirilli A., Citti L., Colombo M.G., Poliseno L., Rainaldi G: Istituto di Fisiologia Clinica del CNR di Pisa. (literal)
Titolo
  • The sensitivity of MCF10A breast epithelial cells to alkylating drugs is enhanced by the inhibition of O-6 methylguanine-DNA methyltransferase transcription with a synthetic double strand DNA oligonucleotide (literal)
Abstract
  • Cytoxicity of alkylating chemotherapeutic drugs is affected by the cellular content of the enzyme O6_ methylguanine-DNA methyl transferase (MGMT). Since high levels of the enzyme confer the efficient repair of DNA alkylation, the chemotherapeutic potential of alkylating chemicals can be maintained either increasing drug dosage or reducing the amount of endogenous MGMT. This study strives to the latter end by competing away a transcriptional activator of the MGMT gene from its native enhancer sequence using a synthetic double strand DNA oligonucleotide (MEBP-ODN). MEBP-ODN was administered in culture medium to MCF10A human breast epithelial cells expressing high level of MGMT. Reverse transcription-polymerase chain reaction and western blotting analyses showed decrease in both MGMT mRNA and protein content. Concomitantly, MEBP-ObN exposed cells were more sensitive to the alkylating drug mitozolomide than their controls, which were not exposed to MEBP-ODN. These results indicate that the cis-acting MEBP-ODN can efficiently deplete MGMT protein by working as decoy binding site for the transcriptional activator MEBP. This approach represents a successful strategy to counteract the protective role of MGMT repair enzyme during an alkylating drug based chemotherapeutic regimen (literal)
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