Multiple mechanisms underlying acquired resistance to taxanes in selected docetaxel-resistant MCF-7 breast cancer cells
Bibliographic record
Abstract
BACKGROUND: Chemoresistance is a major factor involved in a poor response and reduced overall survival in patients with advanced breast cancer. Although extensive studies have been carried out to understand the mechanisms of chemoresistance, many questions remain unanswered. METHODS: In this research, we used two isogenic MCF-7 breast cancer cell lines selected for resistance to doxorubicin (MCF-7DOX) or docetaxel (MCF-7TXT) and the wild type parental cell line (MCF-7CC) to study mechanisms underlying acquired resistance to taxanes in MCF-7TXT cells. Cytotoxicity assay, immunoblotting, indirect immunofluorescence and live imaging were used to study the drug resistance, the expression levels of drug transporters and various tubulin isoforms, apoptosis, microtubule formation, and microtubule dynamics. RESULTS: MCF-7TXT cells were cross resistant to paclitaxel, but not to doxorubicin. MCF-7DOX cells were not cross-resistant to taxanes. We also showed that multiple mechanisms are involved in the resistance to taxanes in MCF-7TXT cells. Firstly, MCF-7TXT cells express higher level of ABCB1. Secondly, the microtubule dynamics of MCF-7TXT cells are weak and insensitive to the docetaxel treatment, which may partially explain why docetaxel is less effective in inducing M-phase arrest and apoptosis in MCF-7TXT cells in comparison with MCF-7CC cells. Moreover, MCF-7TXT cells express relatively higher levels of β2- and β4-tubulin and relatively lower levels of β3-tubulin than both MCF-7CC and MCF-7DOX cells. The subcellular localization of various β-tubulin isoforms in MCF-7TXT cells is also different from that in MCF-7CC and MCF-7DOX cells. CONCLUSION: Multiple mechanisms are involved in the resistance to taxanes in MCF-7TXT cells. The high expression level of ABCB1, the specific composition and localization of β-tubulin isoforms, the weak microtubule dynamics and its insensitivity to docetaxel may all contribute to the acquired resistance of MCF-7TXT cells to taxanes.
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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) | 0.001 | 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 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".