title: Bioenergetic differences between MCF-7 and T47D breast cancer cells and their regulation by oestradiol and tamoxifen.
abstract: Oestrogen receptor α (ERα+) breast tumours rely on mitochondria (mt) to generate ATP. The goal of the present study was to determine how oestradiol (E2) and 4-hydroxytamoxifen (4-OHT) affect cellular bioenergetic function in MCF-7 and T47D ERα+ breast cancer cells in serum-replete compared with dextran-coated charcoal (DCC)-stripped foetal bovine serum (FBS)-containing medium ('serum-starved'). Serum-starvation reduced oxygen consumption rate (OCR), extracellular acidification rate (ECAR), ATP-linked OCR and maximum mt capacity, reflecting lower ATP demand and mt respiration. Cellular respiratory stateapparent was unchanged by serum deprivation. 4-OHT reduced OCR independent of serum status. Despite having a higher mt DNA/nuclear DNA ratio than MCF-7 cells, T47D cells have a lower OCR and ATP levels and higher proton leak. T47D express higher nuclear respiratory factor-1 (NRF-1) and NRF-1-regulated, nuclear-encoded mitochondrial transcription factor TFAM and cytochrome c, but lower levels of cytochrome c oxidase, subunit IV, isoform 1 (COX4, COX4I1). Mitochondrial reserve capacity, reflecting tolerance to cellular stress, was higher in serum-starved T47D cells and was increased by 4-OHT, but was decreased by 4-OHT in MCF-7 cells. These data demonstrate critical differences in cellular energetics and responses to 4-OHT in these two ERα+ cell lines, likely reflecting cancer cell avoidance of apoptosis.
authors.affiliation: *Department of Biochemistry & Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, U.S.A.
authors.forename: Brandie N
authors.initials: BN
authors.lastname: Radde
authors.affiliation: *Department of Biochemistry & Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, U.S.A.
authors.forename: Margarita M
authors.initials: MM
authors.lastname: Ivanova
authors.affiliation: *Department of Biochemistry & Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, U.S.A.
authors.forename: Huy Xuan
authors.initials: HX
authors.lastname: Mai
authors.affiliation: †Deptartment of Medicine, University of Louisville School of Medicine, Louisville, KY 40292, U.S.A.
authors.forename: Joshua K
authors.initials: JK
authors.lastname: Salabei
authors.affiliation: †Deptartment of Medicine, University of Louisville School of Medicine, Louisville, KY 40292, U.S.A.
authors.forename: Bradford G
authors.initials: BG
authors.lastname: Hill
authors.affiliation: *Department of Biochemistry & Molecular Biology, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40292, U.S.A.
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Klinge
mesh_terms: D000143:Acids / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016895:Culture Media, Serum-Free; D004272:DNA, Mitochondrial / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000143:Acids; D016895:Culture Media, Serum-Free; D004272:DNA, Mitochondrial; D009363:Neoplasm Proteins; D013629:Tamoxifen; C016601:afimoxifene; D004958:Estradiol; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate