title: Breast cancer, side population cells and ABCG2 expression.
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.
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle-upon-Tyne NE1 3BZ, UK.
authors.forename: K M
authors.initials: KM
authors.lastname: Britton
authors.affiliation: Institute of Cellular Medicine, The Medical School, Newcastle University, 3rd Floor William Leech Building, Framlington Place, Newcastle-upon-Tyne NE2 4HH, UK.
authors.forename: R
authors.initials: R
authors.lastname: Eyre
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle-upon-Tyne NE1 3BZ, UK.
authors.forename: I J
authors.initials: IJ
authors.lastname: Harvey
authors.affiliation: Department of Systems Biology, University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: K
authors.initials: K
authors.lastname: Stemke-Hale
authors.affiliation: Queen Elizabeth Hospital, Sheriff Hill, Gateshead, UK.
authors.forename: D
authors.initials: D
authors.lastname: Browell
authors.affiliation: Northern Institute of Cancer Research, Newcastle University, Paul O'Gorman Building, Medical School, Framlington Place, Newcastle-upon-Tyne NE2 4HH, UK.
authors.forename: T W J
authors.initials: TWJ
authors.lastname: Lennard
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle-upon-Tyne NE1 3BZ, UK; North East England Stem Cell Institute, Bioscience Centre, International Centre for Life, Central Parkway, Newcastle-upon-Tyne NE1 4EP, UK. Electronic address: annette.meeson@ncl.ac.uk.
authors.forename: A P
authors.initials: AP
authors.lastname: Meeson
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis*; D015415:Biomarkers / Q000032:analysis*; D044963:Biopsy, Fine-Needle; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058985:Side-Population Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D015415:Biomarkers; D009363:Neoplasm Proteins