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Ets-1 regulates energy metabolism in cancer cells.

Verschoor ML, Wilson LA, Verschoor CP, Singh G - PLoS ONE (2010)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Research, Juravinski Cancer Centre, Hamilton, Ontario, Canada.

ABSTRACT
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.

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Generation of an ovarian cancer cell model for Ets-1 expression.2008 ovarian cancer cells were stably transfected to over-express Ets-1 in a tetracycline inducible system. Protein expression of 2008 and 2008-Ets1 cells was measured via Western blot following induction with tetracycline (n = 3).
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pone-0013565-g001: Generation of an ovarian cancer cell model for Ets-1 expression.2008 ovarian cancer cells were stably transfected to over-express Ets-1 in a tetracycline inducible system. Protein expression of 2008 and 2008-Ets1 cells was measured via Western blot following induction with tetracycline (n = 3).

Mentions: Ets-1 was over-expressed in 2008 ovarian cancer cells using a tetracycline-inducible system, generating 2008-Ets1 cells. Ets-1 protein expression in tetracycline-treated 2008 and 2008-Ets1 was examined via Western blotting (Figure 1). Ets-1 protein expression was not detectable in 2008 whole cell lysates, but was readily detected in the induced 2008-Ets1 lysate. Increased Ets-1 expression was found to be a specific effect as the protein levels of two similar Ets family members, Ets-2 and PEA3 were not altered in this model of Ets-1 over-expression (Figure 2).


Ets-1 regulates energy metabolism in cancer cells.

Verschoor ML, Wilson LA, Verschoor CP, Singh G - PLoS ONE (2010)

Generation of an ovarian cancer cell model for Ets-1 expression.2008 ovarian cancer cells were stably transfected to over-express Ets-1 in a tetracycline inducible system. Protein expression of 2008 and 2008-Ets1 cells was measured via Western blot following induction with tetracycline (n = 3).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2962648&req=5

pone-0013565-g001: Generation of an ovarian cancer cell model for Ets-1 expression.2008 ovarian cancer cells were stably transfected to over-express Ets-1 in a tetracycline inducible system. Protein expression of 2008 and 2008-Ets1 cells was measured via Western blot following induction with tetracycline (n = 3).
Mentions: Ets-1 was over-expressed in 2008 ovarian cancer cells using a tetracycline-inducible system, generating 2008-Ets1 cells. Ets-1 protein expression in tetracycline-treated 2008 and 2008-Ets1 was examined via Western blotting (Figure 1). Ets-1 protein expression was not detectable in 2008 whole cell lysates, but was readily detected in the induced 2008-Ets1 lysate. Increased Ets-1 expression was found to be a specific effect as the protein levels of two similar Ets family members, Ets-2 and PEA3 were not altered in this model of Ets-1 over-expression (Figure 2).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Research, Juravinski Cancer Centre, Hamilton, Ontario, Canada.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus