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

A. E. Peaston, M. Gardaneh, A. V. Franco, J. E. Hocker, K. M. Murphy, M. L. Farnsworth, D. R. Catchpoole, M. Haber, M. D. Norris, R. B. Lock, G. M. Marshall

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1564-1571
Number of pages8
JournalBritish Journal of Cancer
Volume85
Issue number10
DOIs
StatePublished - Nov 16 2001
Externally publishedYes

Keywords

  • Apoptosis
  • Bcl-2
  • MRP1
  • Neuritic differentiation
  • Neuroblastoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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  • Cite this

    Peaston, A. E., Gardaneh, M., Franco, A. V., Hocker, J. E., Murphy, K. M., Farnsworth, M. L., Catchpoole, D. R., Haber, M., Norris, M. D., Lock, R. B., & Marshall, G. M. (2001). MRP1 gene expression level regulates the death and differentiation response of neuroblastoma cells. British Journal of Cancer, 85(10), 1564-1571. https://doi.org/10.1054/bjoc.2001.2144