Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation.
The transcription factor Gata-3 is a defining marker of the 'luminal' subtypes of breast cancer. To gain insight into the role of Gata-3 in breast epithelial development and oncogenesis, we have explored its normal function within the mammary gland by conditionally deleting Gata-3 at different stages of development. We report that Gata-3 has essential roles in the morphogenesis of the mammary gland in both the embryo and adult. Through the discovery of a novel marker (beta3-integrin) of luminal progenitor cells and their purification, we demonstrate that Gata-3 deficiency leads to an expansion of luminal progenitors and a concomitant block in differentiation. Remarkably, introduction of Gata-3 into a stem cell-enriched population induced maturation along the alveolar luminal lineage. These studies provide evidence for the existence of an epithelial hierarchy within the mammary gland and establish Gata-3 as a critical regulator of luminal differentiation.
Asselin-Labat
Marie-Liesse
ML
VBCRC Laboratory, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
Sutherland
Kate D
KD
Barker
Holly
H
Thomas
Richard
R
Shackleton
Mark
M
Forrest
Natasha C
NC
Hartley
Lynne
L
Robb
Lorraine
L
Grosveld
Frank G
FG
van der Wees
Jacqueline
J
Lindeman
Geoffrey J
GJ
Visvader
Jane E
JE
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D050990:GATA3 Transcription Factor / Q000172:deficiency / Q000378:metabolism* / Q000494:pharmacology; D039661:Integrin beta3 / Q000096:biosynthesis; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D051379:Mice; D009024:Morphogenesis / Q000187:drug effects*; D011247:Pregnancy; D013234:Stem Cells / Q000378:metabolism
D050990:GATA3 Transcription Factor; D039661:Integrin beta3