Cooperativity of the MUC1 oncoprotein and STAT1 pathway in poor prognosis human breast cancer

Oncogene. 2010 Feb 11;29(6):920-9. doi: 10.1038/onc.2009.391. Epub 2009 Nov 16.


Signal transducer and activator of transcription 1 (STAT1) is activated in the inflammatory response to interferons. The MUC1 oncoprotein is overexpressed in human breast cancers. Analysis of genes differentially expressed in MUC1-transformed cells has identified a network linking MUC1 and STAT1 that is associated with cellular growth and inflammation. The results further show that the MUC1-C subunit associates with STAT1 in cells and the MUC1-C cytoplasmic domain binds directly to the STAT1 DNA-binding domain. The interaction between MUC1-C and STAT1 is inducible by IFNgamma in non-malignant epithelial cells and constitutive in breast cancer cells. Moreover, the MUC1-STAT1 interaction contributes to the activation of STAT1 target genes, including MUC1 itself. Analysis of two independent databases showed that MUC1 and STAT1 are coexpressed in about 15% of primary human breast tumors. Coexpression of MUC1 and the STAT1 pathway was found to be significantly associated with decreased recurrence-free and overall survival. These findings indicate that (i) MUC1 and STAT1 function in an auto-inductive loop, and (ii) activation of both MUC1 and the STAT1 pathway in breast tumors confers a poor prognosis for patients.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cytoplasm / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Humans
  • Interferon-gamma / pharmacology
  • Mammary Glands, Human / drug effects
  • Mammary Glands, Human / metabolism
  • Mammary Glands, Human / pathology
  • Mice
  • Molecular Sequence Data
  • Mucin-1 / chemistry
  • Mucin-1 / genetics
  • Mucin-1 / metabolism*
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • Protein Structure, Tertiary
  • Rats
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism*
  • Signal Transduction* / drug effects


  • MUC1 protein, human
  • Mucin-1
  • STAT1 Transcription Factor
  • Interferon-gamma