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  • Original Paper
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Muc1 affects c-Src signaling in PyV MT-induced mammary tumorigenesis

Oncogene volume 24, pages 5799–5808 (2005)Cite this article

Abstract

MUC1 is an integral membrane mucin glycoprotein that is normally expressed on the apical surface of most simple, secretory epithelia and hematopoietic cells. Overexpression of aberrantly glycosylated MUC1 is a hallmark of many carcinomas including 90% of breast carcinomas. MUC1 has been shown to bind to c-Src tyrosine kinase in vitro, whereby c-Src phosphorylates the MUC1 cytoplasmic domain at a YEKV motif. c-Src is an extensively studied nonreceptor tyrosine kinase implicated in mammary tumorigenesis. Previously, mouse mammary tumor virus-driven polyoma middle T-antigen (MMTV-PyV MT) transgenic mice crossed onto a Muc1 null background exhibited a significant delay in tumor progression. c-Src has been shown to interact with PyV MT, and to play an integral and indispensable role in MMTV-PyV MT-induced mammary tumorigenesis. Here, we determine the effect of Muc1 expression on c-Src activation and signaling. Examination of MMTV-PyV MT glands on a wild-type or Muc1 null background demonstrates that Muc1 expression promotes c-Src signaling by influencing its association with known substrates such as the p85 subunit of phosphatidylinositol 3-kinase and β-catenin. These findings may provide a mechanism for the delay in tumor progression that is observed in the absence of Muc1.

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Acknowledgements

We are grateful to Dr William Muller for the transgenic MMTV-PyV MT mice. We thank Dr Sarah Parsons for the c-Src (2–17) antibody. We thank Stephanie Velgos, Kari Kotlarczyk, and Cathy Madsen for help with generating the mice. We thank Suresh Savarirayan and the animal care attendants for excellent animal care, Marvin H Ruona for computer graphics, and Carol Williams for manuscript assistance. We thank Christine Hattrup for valuable discussions of the manuscript. This work was supported by NIH RO1CA64389 (SJG), DOD Breast Cancer Research Program DAMD17-02-1-0476 (AAM), and Mayo Foundation.

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  1. Department of Biochemistry and Molecular Biology, Mayo Clinic, Scottsdale, 85259, AZ, USA

    Azzah Al Masri & Sandra J Gendler

  2. Tumor Biology Program, Mayo Clinic College of Medicine, Mayo Clinic, Scottsdale, 85259, AZ, USA

    Sandra J Gendler

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  1. Azzah Al Masri
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  2. Sandra J Gendler
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Correspondence to Sandra J Gendler.

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Al Masri, A., Gendler, S. Muc1 affects c-Src signaling in PyV MT-induced mammary tumorigenesis. Oncogene 24, 5799–5808 (2005). https://doi.org/10.1038/sj.onc.1208738

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