Insights from transgenic mouse models of ERBB2-induced breast cancer

Abstract

One-third of patients with breast cancer overexpress the ERBB2 receptor tyrosine kinase, which is associated not only with a more aggressive phenotype but also reduced responsiveness to hormonal therapies. Over the past two decades, many ERBB2 mouse models for breast cancer have conclusively shown that this receptor has a causal role in breast cancer development. These mouse models have also enabled the mechanisms controlling tumour growth, angiogenesis, metastasis, dormancy and recurrence in ERBB2-positive breast cancer to be elucidated. In addition, a mouse model has recently been described that accurately recapitulates many of the hallmarks associated with the early stages of the human disease.

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Figure 1: Generation of oncogenic ERBB2 variants by somatic mutation or alternative splicing.
Figure 2: Signalling pathways that regulate ERBB2-mediated transformation.
Figure 3: Comparison of the MMTV–NEU-NDL and the knock-in mouse model.
Figure 4: Similarity between the ERBB2 amplicons in knock-in-derived mammary tumours and primary human breast cancer.
Figure 5: A histological comparison of ERBB2-based mouse models with ERBB2-positive human breast cancer.

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Acknowledgements

We gratefully acknowledge the following funding agencies for their support: Department of Defense Breast Cancer Research Centers of Excellence (DOD), Canadian Institute of Health Research (CIHR), National Cancer Institute of Canada (NCIC-Terry Fox Group Grant), The Cancer Research Society (CRS), Canadian Breast Cancer Research Alliance (CBCRA) and US National Institutes of Health (NIH).

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Correspondence to William J. Muller.

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Ursini-Siegel, J., Schade, B., Cardiff, R. et al. Insights from transgenic mouse models of ERBB2-induced breast cancer. Nat Rev Cancer 7, 389–397 (2007). https://doi.org/10.1038/nrc2127

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