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- Title
MRP1 gene expression level regulates the death and differentiation response of neuroblastoma cells.
- Authors
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
- 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 ofMRP1 in 2 different NB tumour cell lines by stably transfecting anMRP1 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-lengthMRP1 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.
- Subjects
NEUROBLASTOMA; GENE expression
- Publication
British Journal of Cancer, 2001, Vol 85, Issue 10, p1564
- ISSN
0007-0920
- Publication type
Article
- DOI
10.1054/bjoc.2001.2144