Document Detail


Breast cancer resistance protein (BCRP/ABCG2) localises to the nucleus in glioblastoma multiforme cells.
MedLine Citation:
PMID:  22401348     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Prateek Bhatia; Michel Bernier; Mitesh Sanghvi; Ruin Moaddel; Roland Schwarting; Anuradha Ramamoorthy; Irving W Wainer
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Publication Detail:
Type:  Journal Article     Date:  2012-03-08
Journal Detail:
Title:  Xenobiotica; the fate of foreign compounds in biological systems     Volume:  42     ISSN:  1366-5928     ISO Abbreviation:  Xenobiotica     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-09     Completed Date:  2013-02-04     Revised Date:  2013-08-14    
Medline Journal Info:
Nlm Unique ID:  1306665     Medline TA:  Xenobiotica     Country:  England    
Other Details:
Languages:  eng     Pagination:  748-55     Citation Subset:  IM    
Affiliation:
Laboratory of Clinical Investigation, National Institute on Aging-NIA/NIH, Baltimore, MD, USA.
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / 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
Grant Support
ID/Acronym/Agency:
ZIA AG000296-10/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/ABCG2 protein, human; 0/Indoles; 0/Neoplasm Proteins; 0/RNA, Small Interfering; 55387-45-6/tryptoquivaline; 65271-80-9/Mitoxantrone
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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