Abstract 267: E2F1 regulates human TRAIL promoter and mediates Interferon alpha 2a response
Bibliographic record
Abstract
Abstract The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/APO2L) is a member of the TNF gene superfamily that induces apoptosis upon engagement of cognate death receptors. While TRAIL is relatively non-toxic to normal cells, it selectively induces apoptosis in many transformed cells and has been explored as an anti-cancer agent. Earlier studies have shown the upstream region of human TRAIL gene, contain NFAT, AP-1, and Sp1 binding sites which have been shown to regulate expression of multiple cytokines, but the transcriptional regulation of TRAIL has not yet been elucidated in detail. An examination of the human TRAIL promoter showed the presence of five binding sites for the E2F transcription factors. E2F1 is a transcription factor that plays a well-documented role in cell cycle regulation, differentiation and senescence. In addition to its proliferative effects, E2F1 has been shown to have potent apoptotic properties as well, under appropriate conditions. E2F1 can induce apoptosis via several p53-dependent or -independent mechanisms, either through direct transactivation of proapoptotic genes such as p73, apaf-1 (apoptosis protease-activating factor 1) and caspases or transcriptional repression. Studies presented here show that the human TRAIL promoter is E2F responsive in multiple lung cancer cell lines. Chromatin immunoprecipitation assays showed the recruitment of E2F1 as well as Rb to the TRAIL promoter and transient transfection of E2F1 could induce the expression of a TRAIL-luciferase reporter construct. TRAIL could be repressed by Rb, but this repression could be overcome by the transient transfection of ASK-1, Raf-1 or p38 kinases as well as cycling D or E, suggesting that this promoter is responsive to extracellular signals that can regulate Rb function. It has been shown that stimulation of natural killer cells by Interferon alpha-2a leads to upregulated TRAIL expression. We find that Interferon alpha 2a (IFN α 2a) stimulated lung cancer cell lines exhibited high TRAIL luciferase activity and depletion of E2F1 by siRNA techniques prevented the induction of TRAIL. These results suggest that E2F1 as a critical regulator of TRAIL expression and might facilitate death-receptor-mediated apoptosis. These observations raise the possibility that E2F-mediated regulation of TRAIL might have effects on the immune response of lung cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 267. doi:10.1158/1538-7445.AM2011-267
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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) | 0.001 | 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) | 0.007 | 0.004 |
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".