title: Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation.
abstract: 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.
authors.affiliation: VBCRC Laboratory, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
authors.forename: Marie-Liesse
authors.initials: ML
authors.lastname: Asselin-Labat
authors.forename: Kate D
authors.initials: KD
authors.lastname: Sutherland
authors.forename: Holly
authors.initials: H
authors.lastname: Barker
authors.forename: Richard
authors.initials: R
authors.lastname: Thomas
authors.forename: Mark
authors.initials: M
authors.lastname: Shackleton
authors.forename: Natasha C
authors.initials: NC
authors.lastname: Forrest
authors.forename: Lynne
authors.initials: L
authors.lastname: Hartley
authors.forename: Lorraine
authors.initials: L
authors.lastname: Robb
authors.forename: Frank G
authors.initials: FG
authors.lastname: Grosveld
authors.forename: Jacqueline
authors.initials: J
authors.lastname: van der Wees
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Lindeman
authors.forename: Jane E
authors.initials: JE
authors.lastname: Visvader
mesh_terms: 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
chemical_list: D050990:GATA3 Transcription Factor; D039661:Integrin beta3