Abstract 2313: Role of ferritin dysregulation in human breast cancer cells
Bibliographic record
Abstract
Abstract Breast cancer is the most common malignancy in women. Successful treatment of breast cancer relies on a better understanding of the molecular mechanisms involved in breast cancer initiation and progression. Recent studies have suggested a crucial role of perturbations in ferritin levels and tightly associated with this, the deregulation of intracellular iron homeostasis; however, the underlying molecular mechanisms for the cancer-linked ferritin alterations remain largely unknown and often with conflicting conclusions. Therefore, the present study was undertaken to define the role of ferritin in breast cancer. We determined that human breast cancer cells with an epithelial phenotype, such as MCF-7, MDA-MB-361, and T-47D cells, expressed low levels of ferritin light chain (FTL), ferritin heavy chain (FTH1), transferrin (Tf), iron regulatory protein 1 (IRP1), and IRP-2. In contrast, expression of these proteins was substantially elevated in breast cancer cells with an aggressive mesenchymal phenotype, such as Hs-578T, BT-549, and especially MDA-MB-231 cells. The up-regulation of FTH1 and FTL in MDA-MB-231 cells was accompanied by alterations in the subcellular distribution of these proteins as characterized by an increased level of nuclear ferritin and a lower level of the cellular labile iron pool as compared to MCF-7 cells. We established that FTH1 is a target of miR-200b, suggesting that FTH1 up-regulation in MDA-MB-231 cells may be triggered by the low expression of miR-200b. Ectopic up-regulation of miR-200b by transfection of MDA-MB-231 cells with miR-200b substantially decreased the level of FTH1. More importantly, miR-200b-induced down-regulation of ferritin was associated with an increased sensitivity of the MDA-MB-231 cells to the chemotherapeutic agent doxorubicin. These results suggest that perturbations in ferritin levels are associated with the evolution of breast cancer toward a more advanced malignant phenotype. 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 2313.
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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) | 0.002 | 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".