GATA-3 links tumor differentiation and dissemination in a luminal breast cancer model

Cancer Cell. 2008 Feb;13(2):141-52. doi: 10.1016/j.ccr.2008.01.011.


How breast cancers are able to disseminate and metastasize is poorly understood. Using a hyperplasia transplant system, we show that tumor dissemination and metastasis occur in discrete steps during tumor progression. Bioinformatic analysis revealed that loss of the transcription factor GATA-3 marked progression from adenoma to early carcinoma and onset of tumor dissemination. Restoration of GATA-3 in late carcinomas induced tumor differentiation and suppressed tumor dissemination. Targeted deletion of GATA-3 in early tumors led to apoptosis of differentiated cells, indicating that its loss is not sufficient for malignant conversion. Rather, malignant progression occurred with an expanding GATA-3-negative tumor cell population. These data indicate that GATA-3 regulates tumor differentiation and suppresses tumor dissemination in breast cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Animals
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Cell Differentiation*
  • Cell Movement
  • Cell Proliferation
  • Disease Models, Animal
  • Disease Progression
  • Epithelial Cells / pathology
  • Female
  • GATA3 Transcription Factor / deficiency
  • GATA3 Transcription Factor / metabolism*
  • Gene Deletion
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Hyperplasia
  • Immunohistochemistry
  • Mammary Glands, Animal
  • Mice
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Neoplastic Stem Cells / pathology


  • Biomarkers, Tumor
  • GATA3 Transcription Factor