Abstract 3421: Twist1 and clusterin regulate epithelial-mesenchymal transition
Bibliographic record
Abstract
Abstract INTRODUCTION AND OBJECTIVE: Clusterin (CLU) is a stress-activated, cytoprotective molecular chaperone, and is highly expressed in cells surviving apoptotic stimuli and in advanced and treatment-resistant cancers. In addition, CLU has recently been reported to be implicated in epithelial-mesenchymal transition (EMT). Similarly, oncogenic transcription factor Twist1 which binds to E-box (core sequence, 5’-CANNTG-3’) is known to be a master regulator of EMT. Although CLU is known to be transcriptionally activated by heat-shock factor 1, the mechanism CLU expression in EMT is not fully elucidated. This study begins to define mechanism of CLU expression and relevance in EMT of prostate cancer. METHODS: Human prostate cancer PC-3 and LNCaP cells were used to examine whether the manipulation of Twist1 expression affected CLU expression using quantitative real-time PCR, Western blotting and luciferase reporter assay using CLU promoter region. Chromatin-immunoprecipitation (ChIP) assays were used to determine whether Twist1 binds to CLU promoter region. We also examined markers of EMT after treatment with TGF-β1 and manipulation of Twist1/CLU expression. RESULTS: Twist1 overexpression was shown to upregulate CLU expression whereas Twist1 knockdown reduced CLU expression. ChIP assay and luciferase reporter assay revealed that Twist1 was bound to CLU promoter region and regulated CLU transcription. Treatment with TGF-β1, which is known to be an EMT-inducing cytokine, upregulated Twist1 expression followed by CLU expression. Furthermore, CLU knockdown ameliorated EMT induced by TGF-β1 and Twist1. CONCLUSIONS: This study indicates that CLU regulates EMT induced by TGF-β1 and Twist1 in prostate cancer cells. Modulation of CLU expression may be a useful strategy for developing novel therapeutics regulating EMT. 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 3421. doi:10.1158/1538-7445.AM2011-3421
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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 | 0.000 |
| 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) | 0.002 | 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".