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

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

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  • 1Department of Anatomy, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0452, USA.

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.

PMID:
18242514
[PubMed - indexed for MEDLINE]
PMCID:
PMC2262951
Free PMC Article

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