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Insights from transgenic mouse models of ERBB2-induced breast cancer

Nature Reviews Cancer volume 7, pages 389–397 (2007)Cite this article

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.

References

  1. Shih, C., Padhy, L. C., Murray, M. & Weinberg, R. A. Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts. Nature 290, 261–264 (1981).

    Article  CAS  PubMed  Google Scholar 

  2. Schechter, A. L. et al. The neu oncogene: an erb-B-related gene encoding a 185, 000-Mr tumour antigen. Nature 312, 513–516 (1984).

    Article  CAS  PubMed  Google Scholar 

  3. Slamon, D. J. et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235, 177–182 (1987).

    Article  CAS  PubMed  Google Scholar 

  4. Muller, W. J., Sinn, E., Pattengale, P. K., Wallace, R. & Leder, P. Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. Cell 54, 105–115 (1988).

    Article  CAS  PubMed  Google Scholar 

  5. Bouchard, L., Lamarre, L., Tremblay, P. J. & Jolicoeur, P. Stochastic appearance of mammary tumors in transgenic mice carrying the MMTV/c-neu oncogene. Cell 57, 931–6 (1989).

    Article  CAS  PubMed  Google Scholar 

  6. Slamon, D. J. et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244, 707–712 (1989).

    Article  CAS  PubMed  Google Scholar 

  7. Romond, E. H. et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N. Engl. J. Med. 353, 1673–1684 (2005).

    Article  CAS  PubMed  Google Scholar 

  8. Piccart-Gebhart, M. J. et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N. Engl. J. Med. 353, 1659–1672 (2005).

    Article  CAS  PubMed  Google Scholar 

  9. Robert, N. et al. Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J. Clin. Oncol. 24, 2786–2792 (2006).

    Article  CAS  PubMed  Google Scholar 

  10. Stewart, T. A., Pattengale, P. K. & Leder, P. Spontaneous mammary adenocarcinomas in transgenic mice that carry and express MTV/myc fusion genes. Cell 38, 627–637 (1984).

    Article  CAS  PubMed  Google Scholar 

  11. Sinn, E. et al. Coexpression of MMTV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: synergistic action of oncogenes in vivo. Cell 49, 465–475 (1987).

    Article  CAS  PubMed  Google Scholar 

  12. Guy, C. T., Cardiff, R. D. & Muller, W. J. Activated neu induces rapid tumor progression. J. Biol. Chem. 271, 7673–7678 (1996).

    Article  CAS  PubMed  Google Scholar 

  13. Lemoine, N. R., Staddon, S., Dickson, C., Barnes, D. M. & Gullick, W. J. Absence of activating transmembrane mutations in the c-erbB-2 proto-oncogene in human breast cancer. Oncogene 5, 237–239 (1990).

    CAS  PubMed  Google Scholar 

  14. Guy, C. T. et al. Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease. Proc. Natl Acad. Sci. USA 89, 10578–10582 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Siegel, P. M., Dankort, D. L., Hardy, W. R. & Muller, W. J. Novel activating mutations in the neu proto-oncogene involved in induction of mammary tumors. Mol. Cell. Biol. 14, 7068–7077 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Siegel, P. M. & Muller, W. J. Mutations affecting conserved cysteine residues within the extracellular domain of Neu promote receptor dimerization and activation. Proc. Natl Acad. Sci. USA 93, 8878–8883 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Siegel, P. M., Ryan, E. D., Cardiff, R. D. & Muller, W. J. Elevated expression of activated forms of Neu/ErbB-2 and ErbB-3 are involved in the induction of mammary tumors in transgenic mice: implications for human breast cancer. EMBO J. 18, 2149–2164 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Chan, R., Muller, W. J. & Siegel, P. M. Oncogenic activating mutations in the neu/erbB-2 oncogene are involved in the induction of mammary tumors. Ann. NY Acad. Sci. 889, 45–51 (1999).

    Article  CAS  PubMed  Google Scholar 

  19. Kwong, K. Y. & Hung, M. C. A novel splice variant of HER2 with increased transformation activity. Mol. Carcinog. 23, 62–68 (1998).

    Article  CAS  PubMed  Google Scholar 

  20. Garrett, T. P. et al. The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors. Mol. Cell 11, 495–505 (2003).

    Article  CAS  PubMed  Google Scholar 

  21. Naidu, R., Yadav, M., Nair, S. & Kutty, M. K. Expression of c-erbB3 protein in primary breast carcinomas. Br. J. Cancer 78, 1385–1390 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Dankort, D. L., Wang, Z., Blackmore, V., Moran, M. F. & Muller, W. J. Distinct tyrosine autophosphorylation sites negatively and positively modulate neu-mediated transformation. Mol. Cell. Biol. 17, 5410–5425 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Dankort, D., Jeyabalan, N., Jones, N., Dumont, D. J. & Muller, W. J. Multiple ErbB-2/Neu phosphorylation sites mediate transformation through distinct effector proteins. J. Biol. Chem. 276, 38921–38928 (2001).

    Article  CAS  PubMed  Google Scholar 

  24. Dankort, D. et al. Grb2 and Shc adapter proteins play distinct roles in Neu (ErbB-2)-induced mammary tumorigenesis: implications for human breast cancer. Mol. Cell. Biol. 21, 1540–1551 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Moody, S. E. et al. Conditional activation of Neu in the mammary epithelium of transgenic mice results in reversible pulmonary metastasis. Cancer Cell 2, 451–461 (2002).

    Article  CAS  PubMed  Google Scholar 

  26. Moody, S. E. et al. The transcriptional repressor Snail promotes mammary tumor recurrence. Cancer Cell 8, 197–209 (2005).

    Article  CAS  PubMed  Google Scholar 

  27. Thiery, J. P. Epithelial-mesenchymal transitions in tumour progression. Nature Rev. Cancer 2, 442–454 (2002).

    Article  CAS  Google Scholar 

  28. de Candia, P. et al. Angiogenesis impairment in Id-deficient mice cooperates with an Hsp90 inhibitor to completely suppress HER2/neu-dependent breast tumors. Proc. Natl Acad. Sci. USA 100, 12337–12342 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Howe, L. R. et al. HER2/neu-induced mammary tumorigenesis and angiogenesis are reduced in cyclooxygenase-2 knockout mice. Cancer Res. 65, 10113–10119 (2005).

    Article  CAS  PubMed  Google Scholar 

  30. Oshima, R. G. et al. Angiogenic acceleration of Neu induced mammary tumor progression and metastasis. Cancer Res. 64, 169–79 (2004).

    Article  CAS  PubMed  Google Scholar 

  31. Rodriguez-Manzaneque, J. C. et al. Thrombospondin-1 suppresses spontaneous tumor growth and inhibits activation of matrix metalloproteinase-9 and mobilization of vascular endothelial growth factor. Proc. Natl Acad. Sci. USA 98, 12485–12490 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Siegel, P. M., Shu, W., Cardiff, R. D., Muller, W. J. & Massague, J. Transforming growth factor b signaling impairs Neu-induced mammary tumorigenesis while promoting pulmonary metastasis. Proc. Natl Acad. Sci. USA 100, 8430–8435 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Muraoka, R. S. et al. Increased malignancy of Neu-induced mammary tumors overexpressing active transforming growth factor β1. Mol. Cell. Biol. 23, 8691–8703 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Muraoka-Cook, R. S. et al. Activated type I TGFβ receptor kinase enhances the survival of mammary epithelial cells and accelerates tumor progression. Oncogene 25, 3408–3423 (2006).

    Article  CAS  PubMed  Google Scholar 

  35. Hutchinson, J. N., Jin, J., Cardiff, R. D., Woodgett, J. R. & Muller, W. J. Activation of Akt-1 (PKB-α) can accelerate ErbB-2-mediated mammary tumorigenesis but suppresses tumor invasion. Cancer Res. 64, 3171–3178 (2004).

    Article  CAS  PubMed  Google Scholar 

  36. Yoeli-Lerner, M. et al. Akt blocks breast cancer cell motility and invasion through the transcription factor NFAT. Mol. Cell 20, 539–550 (2005).

    Article  CAS  PubMed  Google Scholar 

  37. Guo, W. et al. Beta 4 integrin amplifies ErbB2 signaling to promote mammary tumorigenesis. Cell 126, 489–502 (2006).

    Article  CAS  PubMed  Google Scholar 

  38. Julien, S. G. et al. Protein tyrosine phosphatase 1B deficiency or inhibition delays ErbB2-induced mammary tumorigenesis and protects from lung metastasis. Nature Genet. 39, 338–346 (2007).

    Article  CAS  PubMed  Google Scholar 

  39. Reddy, H. K. et al. Cyclin-dependent kinase 4 expression is essential for neu-induced breast tumorigenesis. Cancer Res. 65, 10174–10178 (2005).

    Article  CAS  PubMed  Google Scholar 

  40. Landis, M. W., Pawlyk, B. S., Li, T., Sicinski, P. & Hinds, P. W. Cyclin D1-dependent kinase activity in murine development and mammary tumorigenesis. Cancer Cell 9, 13–22 (2006).

    Article  CAS  PubMed  Google Scholar 

  41. Bowe, D. B., Kenney, N. J., Adereth, Y. & Maroulakou, I. G. Suppression of Neu-induced mammary tumor growth in cyclin D1 deficient mice is compensated for by cyclin E. Oncogene 21, 291–298 (2002).

    Article  CAS  PubMed  Google Scholar 

  42. Bulavin, D. V. et al. Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK-mediated activation of the p16(Ink4a)-p19(Arf) pathway. Nature Genet. 36, 343–350 (2004).

    Article  CAS  PubMed  Google Scholar 

  43. Wulf, G., Garg, P., Liou, Y. C., Iglehart, D. & Lu, K. P. Modeling breast cancer in vivo and ex vivo reveals an essential role of Pin1 in tumorigenesis. EMBO J. 23, 3397–3407 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Li, B., Rosen, J. M., McMenamin-Balano, J., Muller, W. J. & Perkins, A. S. neu/ERBB2 cooperates with p53–172H during mammary tumorigenesis in transgenic mice. Mol. Cell. Biol. 17, 3155–3163 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Hulit, J. et al. p27Kip1 repression of ErbB2-induced mammary tumor growth in transgenic mice involves Skp2 and Wnt/β-catenin signaling. Cancer Res. 66, 8529–8541 (2006).

    Article  CAS  PubMed  Google Scholar 

  46. Cabodi, S. et al. p130Cas as a new regulator of mammary epithelial cell proliferation, survival, and HER2-neu oncogene-dependent breast tumorigenesis. Cancer Res. 66, 4672–4680 (2006).

    Article  CAS  PubMed  Google Scholar 

  47. Katsumata, M. et al. Prevention of breast tumour development in vivo by downregulation of the p185neu receptor. Nature Med. 1, 644–648 (1995).

    Article  CAS  PubMed  Google Scholar 

  48. Dakappagari, N. K., Douglas, D. B., Triozzi, P. L., Stevens, V. C. & Kaumaya, P. T. Prevention of mammary tumors with a chimeric HER-2 B-cell epitope peptide vaccine. Cancer Res. 60, 3782–3789 (2000).

    CAS  PubMed  Google Scholar 

  49. Sakai, Y. et al. Vaccination by genetically modified dendritic cells expressing a truncated neu oncogene prevents development of breast cancer in transgenic mice. Cancer Res. 64, 8022–8028 (2004).

    Article  CAS  PubMed  Google Scholar 

  50. Holmgren, L. et al. A DNA vaccine targeting angiomotin inhibits angiogenesis and suppresses tumor growth. Proc. Natl Acad. Sci. USA 103, 9208–9213 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Howe, L. R. et al. Celecoxib, a selective cyclooxygenase 2 inhibitor, protects against human epidermal growth factor receptor 2 (HER-2)/neu-induced breast cancer. Cancer Res. 62, 5405–5407 (2002).

    CAS  PubMed  Google Scholar 

  52. Dang, C. T. et al. Phase II study of celecoxib and trastuzumab in metastatic breast cancer patients who have progressed after prior trastuzumab-based treatments. Clin. Cancer Res. 10, 4062–4067 (2004).

    Article  CAS  PubMed  Google Scholar 

  53. Canney, P. A., Machin, M. A. & Curto, J. A feasibility study of the efficacy and tolerability of the combination of Exemestane with the COX-2 inhibitor Celecoxib in post-menopausal patients with advanced breast cancer. Eur. J. Cancer 42, 2751–2756 (2006).

    Article  CAS  PubMed  Google Scholar 

  54. Liu, M. et al. Antitumor activity of rapamycin in a transgenic mouse model of ErbB2-dependent human breast cancer. Cancer Res. 65, 5325–5336 (2005).

    Article  CAS  PubMed  Google Scholar 

  55. Andrechek, E. R. et al. Amplification of the neu/erbB-2 oncogene in a mouse model of mammary tumorigenesis. Proc. Natl Acad. Sci. USA 97, 3444–3449 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Montagna, C., Andrechek, E. R., Padilla-Nash, H., Muller, W. J. & Ried, T. Centrosome abnormalities, recurring deletions of chromosome 4, and genomic amplification of HER2/neu define mouse mammary gland adenocarcinomas induced by mutant HER2/neu. Oncogene 21, 890–898 (2002).

    Article  CAS  PubMed  Google Scholar 

  57. Hodgson, J. G. et al. Copy number aberrations in mouse breast tumors reveal loci and genes important in tumorigenic receptor tyrosine kinase signaling. Cancer Res. 65, 9695–9704 (2005).

    Article  CAS  PubMed  Google Scholar 

  58. Kauraniemi, P., Kuukasjarvi, T., Sauter, G. & Kallioniemi, A. Amplification of a 280-kilobase core region at the ERBB2 locus leads to activation of two hypothetical proteins in breast cancer. Am. J. Pathol. 163, 1979–1984 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Stein, D. et al. The SH2 domain protein GRB-7 is co-amplified, overexpressed and in a tight complex with HER2 in breast cancer. EMBO J. 13, 1331–1340 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Mano, M. S., Rosa, D. D., De Azambuja, E., Ismael, G. F. & Durbecq, V. The 17q12-q21 amplicon: Her2 and topoisomerase-IIa and their importance to the biology of solid tumours. Cancer Treat. Rev. 33, 64–77 (2007).

    Article  CAS  PubMed  Google Scholar 

  61. Muss, H. B. et al. c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer. N. Engl. J. Med. 330, 1260–1266 (1994).

    Article  CAS  PubMed  Google Scholar 

  62. Pritchard, K. I. et al. HER2 and responsiveness of breast cancer to adjuvant chemotherapy. N. Engl. J. Med. 354, 2103–2111 (2006).

    Article  CAS  PubMed  Google Scholar 

  63. Kingsmore, S. F. et al. Genetic mapping of the mouse topoisomerase II α gene to chromosome 11. Mamm. Genome 4, 288–289 (1993).

    Article  CAS  PubMed  Google Scholar 

  64. Chin, K. et al. Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell 10, 529–541 (2006).

    Article  CAS  PubMed  Google Scholar 

  65. Radany, E. H., Hong, K., Kesharvarzi, S., Lander, E. S. & Bishop, J. M. Mouse mammary tumor virus/v-Ha-ras transgene-induced mammary tumors exhibit strain-specific allelic loss on mouse chromosome 4. Proc. Natl Acad. Sci. USA 94, 8664–8669 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Weaver, Z. A. et al. A recurring pattern of chromosomal aberrations in mammary gland tumors of MMTV-cmyc transgenic mice. Genes Chromosomes Cancer 25, 251–260 (1999).

    Article  CAS  PubMed  Google Scholar 

  67. Hermeking, H. The 14–3-3 cancer connection. Nature Rev. Cancer 3, 931–943 (2003).

    Article  CAS  Google Scholar 

  68. Gunther, K. et al. Differences in genetic alterations between primary lobular and ductal breast cancers detected by comparative genomic hybridization. J. Pathol. 193, 40–47 (2001).

    Article  CAS  PubMed  Google Scholar 

  69. Borg, A., Zhang, Q. X., Olsson, H. & Wenngren, E. Chromosome 1 alterations in breast cancer: allelic loss on 1p and 1q is related to lymphogenic metastases and poor prognosis. Genes Chromosomes Cancer 5, 311–320 (1992).

    Article  CAS  PubMed  Google Scholar 

  70. Bieche, I., Champeme, M. H. & Lidereau, R. A tumor suppressor gene on chromosome 1p32-pter controls the amplification of MYC family genes in breast cancer. Cancer Res. 54, 4274–4276 (1994).

    CAS  PubMed  Google Scholar 

  71. Ferguson, A. T. et al. High frequency of hypermethylation at the 14–3-3 sigma locus leads to gene silencing in breast cancer. Proc. Natl Acad. Sci. USA 97, 6049–6054 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Umbricht, C. B. et al. Hypermethylation of 14–3-3 sigma (stratifin) is an early event in breast cancer. Oncogene 20, 3348–3353 (2001).

    Article  CAS  PubMed  Google Scholar 

  73. Vercoutter-Edouart, A. S. et al. Proteomic analysis reveals that 14–3-3sigma is down-regulated in human breast cancer cells. Cancer Res. 61, 76–80 (2001).

    CAS  PubMed  Google Scholar 

  74. Andrechek, E. R. et al. Gene expression profiling of neu-induced mammary tumors from transgenic mice reveals genetic and morphological similarities to ErbB2-expressing human breast cancers. Cancer Res. 63, 4920–4926 (2003).

    CAS  PubMed  Google Scholar 

  75. Cardiff, R. D. & Wellings, S. R. The comparative pathology of human and mouse mammary glands. J. Mammary Gland. Biol. Neoplasia 4, 105–122 (1999).

    Article  CAS  PubMed  Google Scholar 

  76. Rosner, A. et al. Pathway pathology: histological differences between ErbB/Ras and Wnt pathway transgenic mammary tumors. Am. J. Pathol. 161, 1087–1097 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Dontu, G., Liu, S. & Wicha, M. S. Stem cells in mammary development and carcinogenesis: implications for prevention and treatment. Stem Cell Rev. 1, 207–214 (2005).

    Article  CAS  PubMed  Google Scholar 

  78. Wicha, M. S., Liu, S. & Dontu, G. Cancer stem cells: an old idea-a paradigm shift. Cancer Res. 66, 1883–1890 (2006).

    Article  CAS  PubMed  Google Scholar 

  79. Li, Y. et al. Evidence that transgenes encoding components of the Wnt signaling pathway preferentially induce mammary cancers from progenitor cells. Proc. Natl Acad. Sci. USA 100, 15853–15858 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Shackleton, M. et al. Generation of a functional mammary gland from a single stem cell. Nature 439, 84–88 (2006).

    Article  CAS  PubMed  Google Scholar 

  81. Hortobagyi, G. N. Overview of treatment results with trastuzumab (Herceptin) in metastatic breast cancer. Semin. Oncol. 28, 43–47 (2001).

    Article  CAS  PubMed  Google Scholar 

  82. Pegram, M. & Ngo, D. Application and potential limitations of animal models utilized in the development of trastuzumab (Herceptin): a case study. Adv. Drug Deliv. Rev. 58, 723–734 (2006).

    Article  CAS  PubMed  Google Scholar 

  83. Stocklin, E., Botteri, F. & Groner, B. An activated allele of the c-erbB-2 oncogene impairs kidney and lung function and causes early death of transgenic mice. J. Cell Biol. 122, 199–208 (1993).

    Article  CAS  PubMed  Google Scholar 

  84. Piechocki, M. P., Ho, Y. S., Pilon, S. & Wei, W. Z. Human ErbB-2 (Her-2) transgenic mice: a model system for testing Her-2 based vaccines. J. Immunol. 171, 5787–5794 (2003).

    Article  CAS  PubMed  Google Scholar 

  85. Finkle, D. et al. HER2-targeted therapy reduces incidence and progression of midlife mammary tumors in female murine mammary tumor virus huHER2-transgenic mice. Clin. Cancer Res. 10, 2499–2511 (2004).

    Article  CAS  PubMed  Google Scholar 

  86. Cardiff, R. D. & Muller, W. J. Transgenic mouse models of mammary tumorigenesis. Cancer Surv. 16, 97–113 (1993).

    CAS  PubMed  Google Scholar 

  87. Wagner, K. U. et al. Spatial and temporal expression of the Cre gene under the control of the MMTV-LTR in different lines of transgenic mice. Transgenic Res. 10, 545–553 (2001).

    Article  CAS  PubMed  Google Scholar 

  88. Otten, A. D., Sanders, M. M. & McKnight, G. S. The MMTV LTR promoter is induced by progesterone and dihydrotestosterone but not by estrogen. Mol. Endocrinol. 2, 143–147 (1988).

    Article  CAS  PubMed  Google Scholar 

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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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Authors and Affiliations

  1. and William J. Muller are at the Departments of Medicine and Biochemistry, Josie Ursini-Siegel, Babette Schade, McGill University, Montreal, Quebec, H3A 1A1, Canada.,

    Josie Ursini-Siegel, Babette Schade & William J. Muller

  2. Robert D. Cardiff is at the Department of Pathology, School of Medicine and Center for Comparative Medicine, University of California, Davis, Davis, California, 95616, USA.,

    Robert D. Cardiff

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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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