L'inibizione farmacologia di e2f-1 riduce la proliferazione delle cellule tumorali con un meccanismo p53 - indipendente

Pollutri, Daniela (2014) L'inibizione farmacologia di e2f-1 riduce la proliferazione delle cellule tumorali con un meccanismo p53 - indipendente, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Oncologia e patologia sperimentale, 26 Ciclo. DOI 10.6092/unibo/amsdottorato/6575.
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E2F-1 is a transcription factor that plays a key role in cell-cycle control at G1/S check-point level by regulating the timely expression of many target genes whose products are required for S phase entry and progression. In mammalian cells, E2F-1 is negatively regulated by hypo-phosphorylated Retinoblastoma protein (pRb) whereas it is protected against degradation by its binding to Mouse Double Minute 2 protein (MDM2). In this study we experimented a drug combination in order to obtain a strong down-regulation of E2F-1 by acting on two different mechanisms of E2F-1 regulation mentioned above. This was achieved by combining drugs inhibiting the phosphorylation of pRb with drugs inactivating the MDM2 binding capability. The mechanism of action of these drugs in down-regulating E2F-1 level and activity is p53 independent. As expected, when combined, these drugs strongly inhibits E2F-1 and hinder cell proliferation in p53-/- and p53-mutated cells by blocking them in G1 phase of cell cycle, suggesting that E2F-1 down-regulation may represent a valid chemotherapeutic approach to inhibit proliferation in tumors independently of p53 status.

Tipologia del documento
Tesi di dottorato
Pollutri, Daniela
Dottorato di ricerca
Scuola di dottorato
Scienze biologiche, biomediche e biotecnologiche
Settore disciplinare
Settore concorsuale
Parole chiave
E2F-1, pRb, MDM2, proliferation
Data di discussione
16 Maggio 2014

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