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

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 M...

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Bibliographic Details
Published in:British journal of cancer 2001-11, Vol.85 (10), p.1564-1571
Main 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
Format: Article
Language:English
Subjects:
Acids
Antineoplastic agents
Apoptosis
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Cancer Research
Cell death
Cell Differentiation
Cell Division
Chemotherapy
Clone Cells
Cloning
Cytotoxicity
Dose-Response Relationship, Drug
Down-Regulation
Drug Resistance
Epidemiology
Gene Expression
General aspects
Humans
In Situ Nick-End Labeling
Laboratories
Medical research
Medical sciences
Microscopy, Fluorescence
Molecular Medicine
MRP1 gene
Multidrug Resistance-Associated Proteins - genetics
Multidrug Resistance-Associated Proteins - metabolism
Multidrug Resistance-Associated Proteins - physiology
Neuroblastoma
Neuroblastoma - metabolism
Neuroblastoma - pathology
Oligonucleotides, Antisense - genetics
Oncology
Pharmacology. Drug treatments
Proteins
Proto-Oncogene Proteins c-bcl-2 - metabolism
Regular
regular-article
Transfection
Tretinoin - antagonists & inhibitors
Tumor Cells, Cultured
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Summary: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
ISSN:0007-0920
1532-1827
DOI:10.1054/bjoc.2001.2144