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: Brandie N Radde, Margarita M Ivanova, Huy Xuan Mai, Joshua K Salabei, Bradford G Hill, Carolyn M Klinge
• Journal: The Biochemical journal (Biochem J) Vol. 465 Issue 1 Pg. 49-61 (Jan 01 2015) ISSN: 1470-8728 [Electronic] England
• PMID: 25279503 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Acids
• Culture Media, Serum-Free
• DNA, Mitochondrial
• Neoplasm Proteins
• Tamoxifen
• afimoxifene
• Estradiol
• Adenosine Diphosphate
• Adenosine Triphosphate

Topics

• Acids (metabolism)
• Adenosine Diphosphate (metabolism)
• Adenosine Triphosphate (metabolism)
• Breast Neoplasms (metabolism)
• Cell Nucleus (drug effects, metabolism)
• Cell Proliferation (drug effects)
• Culture Media, Serum-Free
• DNA, Mitochondrial (metabolism)
• Dose-Response Relationship, Drug
• Energy Metabolism (drug effects)
• Estradiol (pharmacology)
• Extracellular Space (drug effects, metabolism)
• Female
• Glycolysis (drug effects)
• Humans
• MCF-7 Cells
• Mitochondria (drug effects, metabolism)
• Neoplasm Proteins (metabolism)
• Oxygen Consumption (drug effects)
• Tamoxifen (analogs & derivatives, pharmacology)
• Time Factors