Regulation of gene expression by glucose metabolism in mammary cell lines

Reprogramming of cancer cell metabolism toward aerobic glycolysis, i.e. the Warburg effect, is a hallmark of cancer; according to current views, the rationale for selecting such energy-inefficient metabolism is the need to increase cellular biomass to sustain production of daughter cells and proliferation. In this view, metabolic reprogramming is considered as a simple phenotypic endpoint that occurs as a consequence of signal transduction mechanisms, including oncogene-driven nutrient uptake and metabolic rewiring. A newly emerging paradigm is instead that transcriptional networks and oncogenic signaling can also be regulated downstream of metabolic pathways, that assume causative roles in controlling cancer cell behavior, above and beyond their core biochemical function. To explore possible links between glucose metabolism and nuclear gene transcription we compared immortalized mammary epithelial cells (MCF10A) and metastatic breast cancer cells (MDA-MB-231) growing in high glucose or in the presence of a widely used inhibitor of glucose uptake / glucose metabolism, 2-deoxy-glucose (2DG). MCF10A or MDA-MB-231 cells growing at low confluence in standard growth conditions were compared to cells incubated for 24 hours with 2-deoxy-glucose (2DG, 50mM) to inhibit glucose metabolism, and then harvested for total RNA extraction. 4 independent biological replicates were performed in parallel for each cell line and experimental condition.