Abstract 216: Role of Akt isoforms in chemoresistance of human endometrial carcinoma cells
Bibliographic record
Abstract
Abstract AKT (also known as PKB) is a crucial survival kinase that is normally activated by growth factors but is constitutively activated at a high frequency in tumors through oncogenic events affecting its upstream regulation. Since studies have demonstrated that the three Akt isoforms exhibit distinct physiological functions, the aim of this study was to determine the isotype-specific functions for Akt in chemoresistance of endometrial carcinoma cells. In order to determine the role of Akt isoforms, we have stably produced transfectants in which the expression of Akt is downregulated by specific shRNAs for each isoforms using the KLE endometrial carcinoma cell line. This endometrial cell line is known to constitutively express the three Akt isoforms and to highly resist to chemotherapeutic treatment. In this study we have demonstrated that stably downregulation of Akt2 by RNA interference severely sensitized KLE cells to cisplatin and induced apoptosis. Moreover, cisplatin treatment of these cells induced the activation of pro-apoptotic factors such as caspase −3 and −9 but also inhibited the expression of anti-apoptotic factors such as XIAP and bcl-2. Alternatively, we used constitutively active Akt expression vectors for each isoform to produce stable transfectants using the chemosensitive Hec 1A endometrial cancer cell lines in which no Akt activity is detected. Constitutive Akt2 expression leads to increase cisplatin resistance in this stable transfectant. Our findings highlight the contribution of Akt2 isoform in the molecular mechanisms that govern chemoresistance of endometrial carcinoma. Furthermore, Akt isoform-specific transfectants will provide a strong model to determine the involvement of each Akt isoforms in chemoresistance of endometrial carcinoma cells. 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 216.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".