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Targeted disruption of Brca1 in restricted compartments of the mouse mammary epithelia

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Abstract

Tumours arising in BRCA1 mutation carriers have a characteristic phenotype, the molecular and cellular basis of which is unknown. To address the hypothesis that this phenotype reflects a role for BRCA1 in either in the basal or the stem cell compartments of the mammary epithelia, we have targeted its disruption to K14 and K6a expressing cells of the mouse. Unlike MMTV and WAP driven conditional knockout models of Brca1, these two models did not result in any observable changes in the mammary gland. Our results suggest that BRCA1-associated tumours arise either in K14 and K6a negative basal cells of the mammary gland, or possibly from transdifferentiation of luminal epithelia.

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Acknowledgements

The authors are grateful to Will Foulkes for helpful discussion, Paul Addison and Tina Chua for assistance with histology, Craig Dickfos and Kym-Kelly Taylor for animal husbandry, and the National Breast Cancer Foundation of Australia and The University of Queensland for funding.

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Authors and Affiliations

  1. School of Molecular and Microbial Sciences, University of Queensland, St. Lucia, QLD, 4072, Australia

    Chanel E. Smart, Kelly M. Brooks, Ashwini Raghavendra, Brooke L. Brewster, Juliet D. French, Joseph A. Rothnagel & Melissa A. Brown

  2. Molecular and Cellular Pathology, School of Medicine, University of Queensland, Herston, QLD, 4006, Australia

    Catherine Clarke & Sunil R. Lakhani

  3. Queensland Institute of Medical Research, Herston, QLD, 4006, Australia

    Catherine Clarke & Sunil R. Lakhani

  4. Institute for Molecular Biosciences, University of Queensland, St. Lucia, QLD, 4072, Australia

    Rehan Hetherington, Joseph A. Rothnagel & Brandon Wainwright

  5. Eskitis Institute of Cell & Molecular Therapies, Griffith University, Nathan Campus, Kessels Road, Nathan, QLD, 4111, Australia

    Jean S. Fleming

Authors
  1. Chanel E. Smart
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  2. Catherine Clarke
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  3. Kelly M. Brooks
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  4. Ashwini Raghavendra
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  5. Brooke L. Brewster
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  6. Juliet D. French
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  7. Rehan Hetherington
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  8. Jean S. Fleming
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  9. Joseph A. Rothnagel
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  10. Brandon Wainwright
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  11. Sunil R. Lakhani
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  12. Melissa A. Brown
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Correspondence to Melissa A. Brown.

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Smart, C.E., Clarke, C., Brooks, K.M. et al. Targeted disruption of Brca1 in restricted compartments of the mouse mammary epithelia. Breast Cancer Res Treat 112, 237–241 (2008). https://doi.org/10.1007/s10549-007-9859-2

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  • DOI: https://doi.org/10.1007/s10549-007-9859-2

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