Examining the Role of ErbB2 in a Mouse Model of Type I Insulin like Growth Factor Receptor-Induced Mammary Tumourigenesis.
Bibliographic record
Abstract
Abstract Background: The type I insulin-like growth factor receptor (IGF-IR) and epidermal growth factor receptor 2 (ErbB2) are both receptor tyrosine kinases extensively implicated in human breast cancer. The IGF-IR is involved in cell proliferation and survival and is overexpressed in a large proportion of breast cancers. Similarly, ErbB2 (Her2) has been identified as a key contributor to a relatively large subset of aggressive breast cancer and is currently the basis for clinical therapeutics. To examine how the IGF-IR contributes to breast cancer and to study this receptor as a potential therapeutic target, we have previously created an inducible transgenic mouse model of IGF-IR overexpression in the mammary gland. In this model, tumours rapidly form upon induction of the transgene, with metastasis to the lung occurring in approximately 25% of animals. In addition, the RM11A cell line was isolated from tumour tissue and was shown to maintain inducible IGF-IR overexpression. The purpose of this study was to examine the interaction between IGF-IR and ErbB2 using our model.Materials and Methods: Protein expression was studied through Western blotting. ErbB2 expression was manipulated through the use of siRNA (for downregulation) and through the use of a plasmid encoding ErbB2 (for upregulation). Stable overexpression of ErbB2 was achieved through transfection of this plasmid with subsequent selection of stable integrants. Tumourigenicity was assessed by direct injection of these cells into the mammary gland. MTT assays and Ki67 staining (through immunofluoresence or immunohistochemistry) were used to examine cell survival and proliferation.Reults: In RM11A cells, survival was impaired upon downregulation and inhibition of ErbB2 in vitro. In our transgenic mouse model, ErbB2 was upregulated in primary tumours overexpressing the IGF-IR and was downregulated upon removal of IGF-IR induction and also in IGF-IR-independent recurrent tumours. In vivo, overexpression of ErbB2 conferred a more aggressive phenotype to RM11A cells. However, ErbB2 overexpression did not enhance proliferation in these cells in vitro or in vivo. The mechanism through which ErbB2 enhances tumourigenesis in or model is currently being investigated.Discussion: ErbB2 appears to have a role in IGF-IR-induced mammary tumourigenesis and can enhance tumour growth. Also, the IGF-IR appears to function in the regulation of ErbB2 in our model. Understanding how these two potent oncogenes interact to promote mammary tumourigenesis will ultimately help in designing treatment regimes specifically targeting the IGF-IR and/or ErbB2. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3156.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".