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.
Hosein Kouros-Mehr  1 ,  Seth K Bechis ,  Euan M Slorach ,  Laurie E Littlepage ,  Mikala Egeblad ,  Andrew J Ewald ,  Sung-Yun Pai ,  I-Cheng Ho ,  Zena Werb
Affiliations
  • 1. Department of Anatomy, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0452, USA.
PMID: 18242514 DOI: 10.1016/j.ccr.2008.01.011
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.

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