MUC1 overexpression results in mammary gland tumorigenesis and prolonged alveolar differentiation

Joyce A. Schroeder, Azzah Al Masri, Melissa C. Adriance, Jennifer C. Tessier, Kari L. Kotlarczyk, Melissa C. Thompson, Sandra J. Gendler

Research output: Contribution to journalArticle

110 Scopus citations

Abstract

MUC1 is a transmembrane mucin that was initially cloned from malignant mammary epithelial cells as a tumor antigen. More than 90% of human breast carcinomas overexpress MUC1. Numerous studies have demonstrated an interaction between MUC1 and other oncogenic proteins such as β-catenin, erbB receptors and c-Src, but a functional role for MUC1 in transformation has not been identified. We previously reported the development of transgenic mice that overexpress human MUC1 in the mouse mammary gland (MMTV-MUC1). Analysis of these transgenic mice at an early age demonstrated the ability of MUC1 to potentiate EGF-dependent activation of MAP kinase signaling pathways in the lactating mammary gland. We now report that multiparous MMTV-MUC1 transgenic mice stochastically develop unifocal mammary gland carcinomas late in life. Molecular analysis of these tumors shows a tumor-specific coimmunoprecipitation between MUC1 and β-catenin. Examination of the contralateral glands in MMTV-MUC1 transgenics demonstrates that the development of frank carcinomas is accompanied by a failure of multiparous glands to undergo postlactational involution. Furthermore, uniparous MMTV-MUC1 transgenic mice display decreased postlactational apoptosis, elevated whey acidic protein expression and aberrant pErk2 activation. These findings are the first to determine that MUC1 overexpression promotes in vivo transformation of the mammary gland.

Original languageEnglish (US)
Pages (from-to)5739-5747
Number of pages9
JournalOncogene
Volume23
Issue number34
DOIs
StatePublished - Jul 29 2004

Keywords

  • Apoptosis
  • Breast cancer
  • Involution
  • Mammary gland
  • Mucin

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    Schroeder, J. A., Al Masri, A., Adriance, M. C., Tessier, J. C., Kotlarczyk, K. L., Thompson, M. C., & Gendler, S. J. (2004). MUC1 overexpression results in mammary gland tumorigenesis and prolonged alveolar differentiation. Oncogene, 23(34), 5739-5747. https://doi.org/10.1038/sj.onc.1207713