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c-Src-null mice exhibit defects in normal mammary gland development and ERα signaling

Oncogene volume 24, pages 5629–5636 (2005)Cite this article

Abstract

The c-Src tyrosine kinase has been implicated to play an integral role in modulating growth factor receptor, integrin and steroid receptor function. One class of steroid receptors that c-Src modulates is the estrogen receptor α (ERα). Although there is strong biochemical evidence supporting a role for c-Src in ERα signaling, the consequence of this association is unclear at the biological level. To explore the significance of c-Src in ERα signaling, we studied the development of various reproductive organs that are dependent on ERα in c-Src-deficient mice. We show that the loss of the c-Src tyrosine kinase correlates with defects in ductal development as well as in uterine and ovarian development. Genetic and biochemical analyses of c-Src-deficient mammary epithelial cells also revealed defects in the ability of mammary epithelial cells to activate a number of signaling pathways in response to exogenous estrogen stimulation. Taken together, these studies demonstrate that c-Src plays a role in ERα signaling in vivo.

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Acknowledgements

We thank Dr P Schwartzberg for the c-Src251 plasmid used in this study. This work was supported by the United States Army Breast Cancer Research Initiative (DAMD17-01-1-0321). H Kim was supported by a scholarship from the Canadian Institutes of Health Research and WJ Muller is a recipient of a CRC Chair in Molecular Oncology.

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Author notes

  1. Harold Kim

    Present address: Sunnybrook and Women's College Health Sciences Centre, Department of Medical Biophysics, University of Toronto, S227-2075 Bayview Avenue, Toronto, Ontario, Canada, M4N 3M5

  2. William Muller

    Present address: Department of Medicine, Molecular Oncology Group, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada, H3A 1A1

Authors and Affiliations

  1. Department of Medical Sciences, McMaster University, 1280 Main Street West, Hamilton, L8S 4K1, Ontario, Canada

    Harold Kim

  2. Department of Biology, McMaster University, 1280 Main Street West, Hamilton, L8S 4K1, Ontario, Canada

    Mike Laing

  3. Department of Pathology & Molecular Medicine, McMaster University, 1280 Main Street West, Hamilton, L8S 4K1, Ontario, Canada

    William Muller

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Correspondence to William Muller.

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Kim, H., Laing, M. & Muller, W. c-Src-null mice exhibit defects in normal mammary gland development and ERα signaling. Oncogene 24, 5629–5636 (2005). https://doi.org/10.1038/sj.onc.1208718

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