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

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

Affiliation

  • 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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