Abstract P1-12-12: The insulin like growth factor axis and development of tamoxifen resistance in breast cancer
Bibliographic record
Abstract
Abstract Background Insulin-like growth factors (IGF). IGFs are potent mitogens for breast epithelial cells that modulate the action of AKT, which has been reported to be associated with tamoxifen resistance. To date, however, anti-IGF strategies have proved disappointing in clinical trials We have investigated whether the IGFBP family of proteins, which modulate the activity of IGF, may play a role in tamoxifen resistance, opening up the route for alternative anti-IGF based therapies. Methodology We investigated the expression of IGF axis genes in parental and tamoxifen-resistant (TamR) MCF-7 cells using qRT-PCR. Gene and protein expression was confirmed using ELISA, Western, and ligand blotting. shRNA transfection was used to silence candidate IGF axis genes in both cell lines. Cell sensitivity 4-hydroxytamoxifen (4-HT) was investigated by WST-1 cell proliferation assay. Results IGF-IR, IGF-2R, IGFBP-2, -4 and -5 genes had the highest expression levels. IGFBP-5 was down-regulated 7-fold while IGFBP-2 was up-regulated by 2-fold in TamR v wt cells. Changes in IGFBP-5 and IGFBP-2 gene expression were mirrored in protein levels measured in conditioned media by ELISA, Western and Ligand blot. Importantly knock down of IGFBP-2 in TamR cells restored sensitivity to 4-HT suggesting a causal role for IGFBP-2 in the acquisition of tamoxifen resistance. Conclusion IGFBP-5 and IGFPB-2 are reciprocally regulated on the acquisition of tamoxifen resistance by MCF-7 cells. Preliminary studies suggest that IGFBP-2 may play a role in the development of tamoxifen resistance in vitro. Citation Format: Yousef M Hawsawi, James Beattie, Reem El-Gendy, Valerie Speirs, Christopher Twelves. The insulin like growth factor axis and development of tamoxifen resistance in breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-12-12.
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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) | 0.005 | 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".