Abstract 43: Role of Ets-1 in the regulation of energy metabolism in cancer cells
Bibliographic record
Abstract
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 (ROS) 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. Microarray analysis of the effects of Ets-1 over-expression in 2008 ovarian cancer cells was conducted using the Affymetrix GeneChip® Human Gene 1.0ST Array. Our findings show that Ets-1 up-regulates key enzymes involved in glycolysis and associated feeder pathways, fatty acid metabolism, and antioxidant defense. Additionally, Ets-1 down-regulates genes involved in the citric acid cycle, electron transport chain, and mitochondrial proteins. These results were validated using real-time qRT-PCR. The mitochondrial activity of both ovarian cancer Ets-1 over-expressing and breast cancer Ets-1 down-regulating cells was evaluated by examining oxygen consumption using various electron transport chain inhibitors (Oxygraph 2k), growth in the absence of glucose, and sensitivity to the glycolytic inhibitor 2-DG. 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 pronounced growth inhibition in a glucose-depleted culture environment. In the context of ROS production, Ets-1 up-regulation induces a significant reduction in H2O2 production, likely due to Ets-1-mediated up-regulation of antioxidants. Collectively, our findings show that Ets-1 is involved in the regulation of cellular metabolism and response to oxidative stress in cancer cells. (This work was supported by operating grants to GS provided by the Canadian Institutes of Health Research) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 43.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".