Cancer cells predominantly utilize glycolysis for ATP production even in the 
presence of abundant oxygen, an environment that would normally result in energy 
production through oxidative phosphorylation. Although the molecular mechanism 
for this metabolic switch to aerobic glycolysis has not been fully elucidated, 
it is likely that mitochondrial damage to the electron transport chain and the 
resulting increased production of reactive oxygen species are significant 
driving forces. In this study, we have investigated the role of the 
transcription factor Ets-1 in the regulation of mitochondrial function and 
metabolism. Ets-1 was over-expressed using a stably-incorporated 
tetracycline-inducible expression vector in the ovarian cancer cell line 2008, 
which does not express detectable basal levels of Ets-1 protein. Microarray 
analysis of the effects of Ets-1 over-expression in these ovarian cancer cells 
shows that Ets-1 up-regulates key enzymes involved in glycolysis and associated 
feeder pathways, fatty acid metabolism, and antioxidant defense. In contrast, 
Ets-1 down-regulates genes involved in the citric acid cycle, electron transport 
chain, and mitochondrial proteins. At the functional level, we have found that 
Ets-1 expression is directly correlated with cellular oxygen consumption whereby 
increased expression causes decreased oxygen consumption. Ets-1 over-expression 
also caused increased sensitivity to glycolytic inhibitors, as well as growth 
inhibition in a glucose-depleted culture environment. Collectively our findings 
demonstrate that Ets-1 is involved in the regulation of cellular metabolism and 
response to oxidative stress in ovarian cancer cells.