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

Azzah Al Masri, Sandra J. Gendler

Research output: Contribution to journalArticle

37 Scopus citations

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 languageEnglish (US)
Pages (from-to)5799-5808
Number of pages10
JournalOncogene
Volume24
Issue number38
DOIs
StatePublished - Sep 1 2005

Keywords

  • Breast cancer
  • Mammary gland
  • Mucin
  • Oncogene
  • Transgenic mice

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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