GATA-3 links tumor differentiation and dissemination in a luminal breast cancer model.
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.
Kouros-Mehr
Hosein
H
Department of Anatomy, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0452, USA.
Bechis
Seth K
SK
Slorach
Euan M
EM
Littlepage
Laurie E
LE
Egeblad
Mikala
M
Ewald
Andrew J
AJ
Pai
Sung-Yun
SY
Ho
I-Cheng
IC
Werb
Zena
Z
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D018450:Disease Progression; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D050990:GATA3 Transcription Factor / Q000172:deficiency / Q000378:metabolism*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006965:Hyperplasia; D007150:Immunohistochemistry; D008321:Mammary Glands, Animal; D051379:Mice; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000473:pathology
D014408:Biomarkers, Tumor; D050990:GATA3 Transcription Factor