Role of radiation induced ß1 – integrin expression in trastuzumab resistance in Her-2 positive breast cancer.
Bibliographic record
Abstract
Abstract Abstract #2014 Problem Statement: Radiation therapy followed by Trastuzumab-based therapy is the standard of care for Her-2 positive breast cancer (BC) patients, but the molecular basis of this sequential treatment has not been investigated. Fifty percent of early BC patients show primary resistance to Trastuzumab (Tz) and 70% of metastatic breast cancer patients develop Tz resistance within one year. Our in vitro pre-clinical data suggests the role of ß1-integrin, a cell adhesion molecule involved in cell survival, invasion and drug resistance, in Tz resistance. Because ionizing radiation (IR) increases the expression of several integrin subunits in endothelial and tumor cells, we hypothesized that radiation induced ß1-integrin expression could be a potential mechanism of Tz resistance in Her-2 positive BC patients. Methods: We use Her-2 positive Tz-senstive BC cell lines, SKBR-3 and BT474, which express lower levels of ß1- integrin, than the Tz-resistant cell line JIMT-1. We analyzed by Immunoblotting the expression of ß1-integrin, phosphorylation and expression of Her-2 and common downstream signaling pathways, PI3-K/Akt and Erk1/2 before and after exposure to IR. Results: Exposure to IR increased ß1-integrin expression in SKBR-3 and BT474 cells, but not in JIMT-1. Increased ß1-integrin expression in BT474 cells was associated with a substantial increase in phosphorlyation of Her-2, suggesting that ß1-inetgrin may induce transactivation of Her-2. Phosphorylation of Erk 1/2 and Akt, important signal transducers for cell proliferation and survival were also increased. We will further, investigate Tz sensitivity of SKBR-3 and BT474 following exposure to IR using a blocking antibody for ß1-integrin, and clonogenic survival and XTT assays to evaluate cellular viability and proliferation. Conclusion: Our results show that IR increased ß1-integrin expression and activation of the PI3-K/Akt pro-survival pathway and suggest that increased b1-integrin expression by IR may confer resistance to Trastuzumab in Her-2 positive cell lines. The physiological relevance of radiation-induced ß1-inetgrin expression in Trastuzumab resistance needs to be further investigated in vivo. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2014.
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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) | 0.003 | 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".