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Targeted disruption of ErbB2/Neu in the mammary epithelium results in impaired ductal outgrowth

Oncogene volume 24, pages 932–937 (2005)Cite this article

Abstract

The ErbB2 receptor tyrosine kinase has been implicated as a critical growth factor receptor in both normal development and cancer. Amplification and overexpression of this receptor is observed in 20–30% of all human breast cancers and is inversely correlated with patient survival. Studies with transgenic mice have established that elevated expression of erbB2 in mammary epithelium can directly induce mammary carcinomas. Although these studies confirmed a role for ErbB2 in breast cancer induction, the precise role of ErbB2 in normal mammary gland development remained to be elucidated due to the embryonic lethality associated with the null mutation. Here, we demonstrate that the mammary-specific ablation of erbB2 through Cre-mediated recombination leads to a striking ductal elongation defect. In addition to the observed elongation defect, we noted that branching in the adult mammary gland was also reduced. Despite these perturbations in virgin mammary gland morphogenesis, targeted disruption of erbB2 had little impact on the ability of these animals to lactate. Taken together, these observations indicate that erbB2 plays a critical role in the initial stages of mammary gland morphogenesis.

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Acknowledgements

This work was supported by a CIHR grant awarded to WJM. WJM is also the recipient of a CRC Chair position. ERA was supported by a DOD predoctoral scholarship during this research – DAMD17-99-1-9285.

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Author notes

  1. Eran R Andrechek

    Present address: Department of Molecular Genetics & Microbiology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC, 27710, USA

  2. Donald White

    Present address: Molecular Oncology Group, McGill University, Royal Victoria Hospital, 687 Pine Ave. W., Montreal, Quebec, Canada, H3A 1A1

Authors and Affiliations

  1. Institute for Molecular Biology and Biotechnology, Department of Biology, McMaster University, Hamilton, L8S 4K1, Canada

    Eran R Andrechek

  2. Department of Medical Science, McMaster University, Hamilton, L8S 4K1, Canada

    Donald White

  3. Molecular Oncology Group, McGill University, Royal Victoria Hospital, 687 Pine Ave. W., Montreal, Quebec, Canada, H3A 1A1

    William J Muller

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  1. Eran R Andrechek
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Correspondence to William J Muller.

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Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc)

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Andrechek, E., White, D. & Muller, W. Targeted disruption of ErbB2/Neu in the mammary epithelium results in impaired ductal outgrowth. Oncogene 24, 932–937 (2005). https://doi.org/10.1038/sj.onc.1208230

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