GATA-3 Links Tumor Differentiation and Dissemination in a Luminal Breast Cancer Model

Hosein Kouros-Mehr, Seth K. Bechis, Euan M. Slorach, Laurie E. Littlepage, Mikala Egeblad, Andrew J. Ewald, Sung Yun Pai, I. Cheng Ho, Zena Werb

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)141-152
Number of pages12
JournalCancer cell
Volume13
Issue number2
DOIs
StatePublished - Feb 5 2008
Externally publishedYes

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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  • Cite this

    Kouros-Mehr, H., Bechis, S. K., Slorach, E. M., Littlepage, L. E., Egeblad, M., Ewald, A. J., Pai, S. Y., Ho, I. C., & Werb, Z. (2008). GATA-3 Links Tumor Differentiation and Dissemination in a Luminal Breast Cancer Model. Cancer cell, 13(2), 141-152. https://doi.org/10.1016/j.ccr.2008.01.011