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

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). pp. 141-152. ISSN 15356108 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/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. © 2008 Elsevier Inc. All rights reserved.

Item Type: Paper
Uncontrolled Keywords: CELLCYCLE transcription factor GATA 3 analytic method animal cell animal experiment animal model apoptosis article bioinformatics breast cancer cancer model carcinoma controlled study gene gene deletion metastasis mouse nonhuman priority journal transcription factor GATA 3 gene tumor differentiation tumor growth Adenocarcinoma Animals Breast Neoplasms Cell Differentiation Cell Movement Cell Proliferation Disease Models, Animal Disease Progression Epithelial Cells Female GATA3 Transcription Factor Gene Expression Profiling Gene Expression Regulation, Neoplastic Hyperplasia Immunohistochemistry Mammary Glands, Animal Mice Neoplasm Metastasis Neoplasm Transplantation Neoplastic Stem Cells Tumor Markers, Biological
Subjects: diseases & disorders > cancer
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
diseases & disorders > cancer > cancer types > breast cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
diseases & disorders > cancer > cancer types
CSHL Authors:
Communities: CSHL labs > Egeblad lab
Depositing User: Matt Covey
Date: 2008
Date Deposited: 14 Mar 2013 19:58
Last Modified: 14 Mar 2013 19:58
PMCID: PMC2262951
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27808

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