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.
Original language | English (US) |
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Pages (from-to) | 5799-5808 |
Number of pages | 10 |
Journal | Oncogene |
Volume | 24 |
Issue number | 38 |
DOIs | |
State | Published - Sep 1 2005 |
Keywords
- Breast cancer
- Mammary gland
- Mucin
- Oncogene
- Transgenic mice
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research