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. 2001 Nov;85(10):1564–1571. doi: 10.1054/bjoc.2001.2144

MRP1 gene expression level regulates the death and differentiation response of neuroblastoma cells

A E Peaston 1, M Gardaneh 1, A V Franco 1, J E Hocker 1, K M Murphy 1, M L Farnsworth 1, D R Catchpoole 1, M Haber 1, M D Norris 1, R B Lock 1, G M Marshall 1,2
PMCID: PMC2363953  PMID: 11720446

Abstract

We have previously reported a strong correlation between poor prognosis in childhood neuroblastoma (NB) patients and high-level expression of the transmembrane efflux pump, Multidrug Resistance-associated Protein (MRP1), in NB tumour tissue. In this study, we inhibited the endogenous expression of MRP1 in 2 different NB tumour cell lines by stably transfecting an MRP1 antisense expression vector (MRP-AS). Compared with control cells, MRP-AS transfectant cells demonstrated a higher proportion of dead and morphologically apoptotic cells, spontaneous neuritogenesis, and, increased synaptophysin and neurofilament expression. Bcl-2 protein expression was markedly reduced in MRP-AS cells compared to controls. Conversely, we found that the same NB tumour cell line overexpressing the full-length MRP1 cDNA in sense orientation (MRP-S) demonstrated resistance to the neuritogenic effect of the differentiating agent, all-trans-retinoic acid. Taken together, the results suggest that the level of MRP1 expression in NB tumour cells may influence the capacity of NB cells for spontaneous regression in vivo through cell differentiation and death. © 2001 Cancer Research Campaign  http://www.bjcancer.com

Keywords: MRP1, neuroblastoma, apoptosis, neuritic differentiation, Bcl-2

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Footnotes

These authors contributed equally to this work.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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