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Mouse models for breast cancer

Oncogene volume 19, pages 966–967 (2000)Cite this article

Fifteen years ago, Philip Leder and his colleagues generated a transgenic mouse that developed mammary tumors as a result of the expression of the human oncogene myc in the mammary epithelium (Stewart et al., 1984). Three years later the same group demonstrated the synergism between different oncoproteins, and thus set the stage for the cooperative and multi-event cancer model (Sinn et al., 1987). These classical papers are milestones in breast cancer research, and they set into motion an ever-accelerating research train poised to explore genetic pathways in breast cancer. Federal and private funding agencies alike saw an opportunity to promote efforts aimed to identify and understand genetic pathways in breast cancer in settings resembling the human condition. A recent study by Xu, and her colleagues (Xu et al., 1999) exemplifies another milestone towards this goal. They succeeded in the inactivation of the breast cancer gene Brca1 specifically in mammary epithelial cells of mice, and demonstrated that these mice developed mammary tumors coinciding with genome instability (see Deng and Scott, this issue).

Understanding genetic pathways was considered to be, and still remains, the prerequisite for the development of molecular and pharmacological therapeutics to treat and prevent cancer. Over the past 15 years the use of transgenic and gene deletion mice in mammary research has been documented in more than 100 scientific articles. These studies have provided an in-depth insight into molecular pathways of both normal mammary development and tumorigenesis. While studies in tissue culture cells permit the molecular dissection of pathways operative in a single cell, research in mice integrates the complexity of an organ and its different cell types with the dynamic hormonal and physiological status of the animal. One important lesson from these studies points to an equally important role of the stroma in the development of the mammary gland (Hennighausen and Robinson, 1998).

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References

  • Hennighausen L and Robinson GW. . 1998 Genes and Development 12: 449–455.

  • Sinn E, Muller W, Pattengale P, Tepler I, Wallace R and Leder P. . 1987 Cell 49: 465–475.

  • Stewart TA, Pattengale PK and Leder P. . 1984 Cell 38: 627–637.

  • Xu X, Wagner KU, Larson D, Weaver Z, Li C, Ried T, Hennighausen L, Wynshaw-Boris A and Deng CX. . 1999 Nat. Genet. 22: 37–43.

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  1. Laboratory of Genetics and Physiology, Building 8, Room 101, National Institute of Diabetes Digestive and Kidney Diseases, National Institutes of Health, Bethesda, 20892, Maryland, MD, USA

    Lothar Hennighausen

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  1. Lothar Hennighausen
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Hennighausen, L. Mouse models for breast cancer. Oncogene 19, 966–967 (2000). https://doi.org/10.1038/sj.onc.1203346

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