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Development of mammary adenocarcinomas by tissue-specific knockout of Brca2 in mice

Oncogene volume 20, pages 3937–3948 (2001)Cite this article

Abstract

Cre-mediated deletion of exons 3 and 4 of the mouse Brca2 gene occurring specifically in mammary epithelial cells of conditional female mutants carrying a combination of loxP-modified and null Brca2 alleles resulted in a high incidence (77%) of breast tumors that were often palpable and developed in one or more glands after long latency (time for median tumor-free survival of ∼1.4 years; total of 40 tumors in 20 animals). These invasive adenocarcinomas were histologically quite uniform, exhibiting predominantly a solid, nodular tumor pattern with very few variants, in striking contrast to the morphological heterogeneity of analogous Brca1-associated tumors. The karyotypes of tumor cells lacking Brca2 had various chromosomal aberrations and ranged from diploid to hypertetraploid, but this wide variability was incongruous with the histological appearance of carcinomas that was comparable between specimens. The implications of these observations in the context of models positing that Brca2 is involved in the maintenance of genomic stability are discussed.

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Acknowledgements

We thank Phil Leder for kindly providing the strain of MMTV-neu transgenic mice, Shouhong Xuan for contributing unpublished information, and Lejuan Chatman, Qiong Li and Mian Su for expert technical assistance. This work was supported by NCI grant P01 CA75553 (Project 3) to A Efstradiadis Additional support to A Efstradiadis and T Ludwig was provided, respectively, by grants to the Herbert Irving Comprehensive Cancer Center of the Columbia Presbyterian Medical Center from the Avon Products Foundation Breast Cancer Research and Care Program and from the American Cancer Society (IRG-177F).

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Columbia University, New York, 10032, NY, USA

    Thomas Ludwig

  2. Department of Pathology, Columbia University, New York, 10032, NY, USA

    Peter Fisher & Vundavalli Murty

  3. Department of Genetics and Development, Columbia University, New York, 10032, NY, USA

    Argiris Efstratiadis

  4. Institute of Cancer Genetics, Columbia University, New York, 10032, NY, USA

    Argiris Efstratiadis

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Correspondence to Thomas Ludwig.

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Ludwig, T., Fisher, P., Murty, V. et al. Development of mammary adenocarcinomas by tissue-specific knockout of Brca2 in mice. Oncogene 20, 3937–3948 (2001). https://doi.org/10.1038/sj.onc.1204512

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