Cisplatin (DDP)-resistance confers a deficient expression of spermidine/spermine N-1-acetyltransferase (SSAT) gene in response to the spermine analog N-1,N-12-bis(ethyl)spermine (BESpm) in the DDP-resistant human ovarian carcinoma cell line (C13*), compared with their parental DDP-sensitive 2008 cells. This SSAT gene deficiency is correlated with a reduced growth sensitivity to spermine analogs. This study was performed to determine whether SSAT gene expression of resistant cells was kept suppressed by labile repressor proteins developed during resistance selection. We show here that inhibitory concentrations of cycloheximide (CHX) and anisomycin (ANISO) differentially affect BESpm-induced SSAT activity in 2008 and in C13* cells in a concentration-dependent manner and allow resistant cells to reach activation levels comparable to those of the sensitive cells. Northern blot analysis revealed that both CHX and ANISO in combination with BESpm caused a synergistic BESpm-mediated accumulation of SSAT mRNA in C13* cells, with respect to each drug alone, while in 2008 cells only a slight increase was observed. The more pronounced effect of inhibitors on the SSAT activity induced by BESpm in the resistant cells was also the result of a more prolonged stabilization of SSAT mRNA and enzyme protein. By contrast, sub-inhibitory concentrations of CHX and ANISO did not significantly stimulate BESpm-induced SSAT transcription and activity. These results suggest that labile repressor proteins, related to DDP-resistance phenotype, play a regulatory role in SSAT gene expression, and further indicate that by overcoming this inhibitory control it is possible to recover BESpm response.
Attenzione! Scheda prodotto non ancora validata dall'Ateneo
Dati e metadati della pubblicazione sono in fase di verifica da parte dell'Ateneo. In caso di errori o violazione dei diritti d'autore, contattare: firstname.lastname@example.org
|Data di pubblicazione:||2004|
|Titolo:||Cisplatin-resistance modulates the effect of protein synthesis inhibitors on spermidine/spermine N-1-acetyltransferase expression|
|Autori:||G. Marverti; MG Monti; S. Bettuzzi; A. Caporali; S. Astancolle; MS Moruzzi|
|Autori interni:||MARVERTI, Gaetano |
MONTI, Maria Giuseppina
MORUZZI, Maria Stella
|Digital Object Identifier (DOI):||10.1016/S1357-2725(03)00174-2|
|Rivista:||THE INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY|
|Appare nelle tipologie:||Articolo su rivista|
I documenti presenti in Iris Unimore sono rilasciati con licenza Creative Commons Attribuzione - Non commerciale - Non opere derivate 3.0 Italia, salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris