title: Muc1 affects c-Src signaling in PyV MT-induced mammary tumorigenesis.
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 beta-catenin. These findings may provide a mechanism for the delay in tumor progression that is observed in the absence of Muc1.
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic, Scottsdale, AZ 85259, USA.
authors.forename: Azzah
authors.initials: A
authors.lastname: Al Masri
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Gendler
mesh_terms: D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D005260:Female; D016391:Genes, src / Q000502:physiology*; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000821:virology; D008324:Mammary Tumor Virus, Mouse; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000952:Antigens, Polyomavirus Transforming; D018396:Mucin-1