GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland.
The GATA family of transcription factors plays fundamental roles in cell-fate specification. However, it is unclear if these genes are necessary for the maintenance of cellular differentiation after development. We identified GATA-3 as the most highly enriched transcription factor in the mammary epithelium of pubertal mice. GATA-3 was found in the luminal cells of mammary ducts and the body cells of terminal end buds (TEBs). Upon conditional deletion of GATA-3, mice exhibited severe defects in mammary development due to failure in TEB formation during puberty. After acute GATA-3 loss, adult mice exhibited undifferentiated luminal cell expansion with basement-membrane detachment, which led to caspase-mediated cell death in the long term. Further, FOXA1 was identified as a downstream target of GATA-3 in the mammary gland. This suggests that GATA-3 actively maintains luminal epithelial differentiation in the adult mammary gland, which raises important implications for the pathogenesis of breast cancer.
Kouros-Mehr
Hosein
H
Department of Anatomy and The Biomedical Sciences Program, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
Slorach
Euan M
EM
Sternlicht
Mark D
MD
Werb
Zena
Z
D000818:Animals; D016923:Cell Death; D002454:Cell Differentiation; D019070:Cell Lineage; D004848:Epithelium / Q000473:pathology; D050990:GATA3 Transcription Factor / Q000172:deficiency / Q000378:metabolism*; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000235:genetics; D007774:Lactation / Q000502:physiology; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000254:growth & development / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic / Q000235:genetics; D013997:Time Factors
C496500:Foxa1 protein, mouse; D050990:GATA3 Transcription Factor; D051541:Hepatocyte Nuclear Factor 3-alpha