Bioenergetic differences between MCF-7 and T47D breast cancer cells and their regulation by estradiol and tamoxifen

Estrogen receptor α (ERα+) breast tumors rely on mitochondria (mt) to generate ATP. The goal of this study was to determine how estradiol (E2) and 4-hydroxytamoxifen (4-OHT) affect cellular bioenergetic function in MCF-7 and T47D ERα+ breast cancer cells in serum-replete versus dextran-coated charcoal (DCC)-stripped fetal 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.

Source: BJ Energy - October 3, 2014 Category: Biochemistry Authors: B N Radde, M M Ivanova, H Xuan Mai, J K Salabei, B G Hill, C M Klinge Tags: BJ Metabolism Source Type: research