AbstractBackground: We have previously shown that expression levels of the multidrug transportersABCC1 and ABCC4, are strongly predictive of outcome in childhood neuroblastoma. Although theprognostic significance of ABCC genes is usually explained in terms of cytotoxic drug resistance, anumber of observations suggested that these multidrug transporters might be contributing to themalignant phenotype independent of cytotoxic drug efflux.Methods: A MYCN-driven transgenic mouse neuroblastoma model was crossed with an Abcc1-deficient mouse strain or alternatively, treated with an ABCC1 inhibitor. ABCC genes weresuppressed using siRNA or overexpressed by stable transfection in neuroblastoma cell lines. Realtimequantitative PCR was used to examine the clinical significance of ABCC family geneexpression in a large prospectively accrued cohort (n=209) of primary neuroblastomas.Results: Pharmacological inhibition or genetic depletion of ABCC1 significantly inhibitedneuroblastoma development in hMYCN transgenic mice (p=0.0005, p

ABCC multidrug transporters in childhood neuroblastoma: clinical and biological effects independent of cytotoxic drug efflux.

Iraci, Nunzio;
2011

Abstract

AbstractBackground: We have previously shown that expression levels of the multidrug transportersABCC1 and ABCC4, are strongly predictive of outcome in childhood neuroblastoma. Although theprognostic significance of ABCC genes is usually explained in terms of cytotoxic drug resistance, anumber of observations suggested that these multidrug transporters might be contributing to themalignant phenotype independent of cytotoxic drug efflux.Methods: A MYCN-driven transgenic mouse neuroblastoma model was crossed with an Abcc1-deficient mouse strain or alternatively, treated with an ABCC1 inhibitor. ABCC genes weresuppressed using siRNA or overexpressed by stable transfection in neuroblastoma cell lines. Realtimequantitative PCR was used to examine the clinical significance of ABCC family geneexpression in a large prospectively accrued cohort (n=209) of primary neuroblastomas.Results: Pharmacological inhibition or genetic depletion of ABCC1 significantly inhibitedneuroblastoma development in hMYCN transgenic mice (p=0.0005, p
ABCC TRANSPORTERS; NEUROBLASTOMA; CHEMORESISTANCE; GENE TRANSCRIPTION; MRP1-KO MICE
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11769/240021
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