The Interaction of PI3K Inhibition with Homologous Recombination Repair in Triple Negative Breast Cancer Cells
Bibliographic record
Abstract
PURPOSE: Aberrant activation of the phosphatidylinositol 3'-kinase (PI3K)-Akt signaling pathway is observed in many types of human cancer including triple negative breast cancer (TNBC). Additionally, dysregulation in the homologous recombination (HR)-dependent DNA-repair is associated with TNBC phenotype due to BRCA1/2 mutations or HR deficiency. Therefore, the hypothesis of this study was to evaluate the association of PI3K inhibition with HR pathway in TNBC in terms of BRCA1 mutation status. METHODS: To examine the potential therapeutic effect of LY294002, an inhibitor of PI3K, on TNBC cell lines with known BRCA1 status, WST-1, annexin V, cell cycle analysis and AO/EB staining were performed. Additionally, RT-PCR and immunofluorescence analysis was used to explore the interaction between the inhibition of PI3K and HR functionality. RESULTS: The findings showed that LY294002 could significantly inhibited the proliferation of TNBC cells. Furthermore, the suppression of PI3K resulted in HR impairment by BRCA1 and RAD51 downregulation and apoptotic cell death by the induction of DNA damage and BAX overexpression. Therefore, LY294002 was more effective in BRCA1-deficient TNBC cells. CONCLUSIONS: Consequently, targeted therapies based on the interaction of PI3K inhibition with BRCA1 mutations or HR deficiency in TNBC may be a promising strategy for the treatment of patients with TNBC.
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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 | 0.001 |
| 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".