| Breast cancer resistance protein (BCRP/ABCG2) localises to the nucleus in glioblastoma multiforme cells. | |
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MedLine Citation:
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PMID: 22401348 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The breast cancer resistance protein (BCRP), an ATP binding cassette (ABC) efflux transporter, plays a role in multiple drug resistance (MDR). Previous studies of the subcellular location of the ABC transporter P-glycoprotein indicated that this protein is expressed in nuclear membranes. This study examines the nuclear distribution of BCRP in seven human-derived glioblastoma (GBM) and astrocytoma cell lines. BCRP expression was observed in the nuclear extracts of 6/7 cell lines. Using the GBM LN229 cell line as a model, nuclear BCRP protein was detected by immunoblotting and confocal laser microscopy. Importantly, nuclear BCRP staining was found in a subpopulation of tumour cells in a human brain GBM biopsy. Mitoxantrone cytotoxicity in the LN229 cell line was determined with and without the BCRP inhibitor fumitremorgin C (FTC) and after downregulation of BCRP with small interfering RNA (siRNA). FTC inhibition of BCRP increased mitoxantrone cytotoxicity with a ~7-fold reduction in the IC₅₀ and this effect was further potentiated in the siRNA-treated cells. In conclusion, BCRP is expressed in the nuclear extracts of select GBM and astrocytoma cell lines and in a human GBM tumour biopsy. Its presence in the nucleus of cancer cells suggests new role for BCRP in MDR. |
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Authors:
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Prateek Bhatia; Michel Bernier; Mitesh Sanghvi; Ruin Moaddel; Roland Schwarting; Anuradha Ramamoorthy; Irving W Wainer |
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Publication Detail:
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Type: Journal Article Date: 2012-03-08 |
Journal Detail:
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Title: Xenobiotica; the fate of foreign compounds in biological systems Volume: 42 ISSN: 1366-5928 ISO Abbreviation: Xenobiotica Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-07-09 Completed Date: 2013-02-04 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 1306665 Medline TA: Xenobiotica Country: England |
Other Details:
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Languages: eng Pagination: 748-55 Citation Subset: IM |
Affiliation:
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Laboratory of Clinical Investigation, National Institute on Aging-NIA/NIH, Baltimore, MD, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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ATP-Binding Cassette Transporters
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antagonists & inhibitors,
metabolism* Astrocytoma / metabolism, pathology Biopsy Brain Neoplasms / metabolism*, pathology* Cell Death / drug effects Cell Line, Tumor Cell Nucleus / drug effects, metabolism* Cell Proliferation / drug effects Chromatography, High Pressure Liquid Fluorescent Antibody Technique Gene Knockdown Techniques Glioblastoma / metabolism*, pathology* Humans Immunoblotting Indoles / analysis, pharmacology Microscopy, Confocal Mitoxantrone / pharmacology Neoplasm Proteins / antagonists & inhibitors, metabolism* Protein Transport / drug effects RNA, Small Interfering / metabolism Subcellular Fractions / drug effects, metabolism |
| Chemical | |
Reg. No./Substance:
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0/ABCG2 protein, human; 0/Indoles; 0/Neoplasm Proteins; 0/RNA, Small Interfering; 55387-45-6/tryptoquivaline; 65271-80-9/Mitoxantrone |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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