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Breast cancer, side population cells and ABCG2 expression

Lookup NU author(s): Dr Kelly Britton, Ian Harvey, Professor Thomas Lennard, Dr Annette Meeson

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Abstract

Recurrent metastatic breast cancer may arise in part due to the presence of drug resistant adult stem cells such as Side Population (SP) cells, whose phenotype has been demonstrated to be due to the expression of ABCG2. We hypothesised that SP may be identified in Fine Needle Aspirates (FNAs) and their presence may be determined by expression of ABCG2 in breast tumours. SP and non-side population cells (NSP) were isolated using dual wavelength flow cytometry combined with Hoechst 33342 dye efflux and analysed for expression of ABCG2 and chemoresistance. FNA samples used in SP analysis were matched with paraffin-embedded tissue which was used in immunohistochemical analysis to assess ABCG2 expression. Results were correlated to the pathobiology of the tumour. MCF7 and MDA-MB-231 cell lines contain SP cells. MCF7 SP have increased expression of ABCG2 and increased resistance to mitoxantrone compared to NSP cells. The presence of SP in FNAs were significantly associated with ER-negative (p=0.008) and with triple negative breast cancers (p=0.011) which were also found to have a significant increase in ABCG2 protein expression. ABCG2 transcript was detected in some but not all SP cell populations isolated from FNA samples.


Publication metadata

Author(s): Britton KM, Eyre R, Harvey IJ, Stemke-Hale K, Browell D, Lennard TWJ, Meeson AP

Publication type: Article

Publication status: Published

Journal: Cancer Letters

Year: 2012

Volume: 323

Issue: 1

Pages: 97-105

Print publication date: 17/04/2012

ISSN (print): 0304-3835

ISSN (electronic): 1872-7980

Publisher: Elsevier Ireland Ltd

URL: http://dx.doi.org/10.1016/j.canlet.2012.03.041

DOI: 10.1016/j.canlet.2012.03.041


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Funding

Funder referenceFunder name
Royal Victoria infirmary, Newcastle-upon-Tyne, UK
Gateshead NHS Trust
RVI Breast Cancer Appeal
KG081099Susan B. Komen Grant

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