Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation

Asselin-Labat, ML; Sutherland, KD; Barker, H; Thomas, R; Shackleton, M; Forrest, NC; Hartley, L; Robb, L; Grosveld, FG; van der Wees, J; Lindeman, GJ; Visvader, JE

Author(s): Asselin-Labat, ML; Sutherland, KD; Barker, H; Thomas, R; Shackleton, M; Forrest, NC; Hartley, L; Robb, L; Grosveld, FG; van der Wees, J; Lindeman, GJ; Visvader, JE;
Details: Publication Year 2007-02,Volume 9,Issue #2,Page 201-U103
Journal Title: NATURE CELL BIOLOGY
Publication Type: Journal Article
Abstract: The transcription factor Gata-3 is a defining marker of the 'luminal' subtypes of breast cancer(1-4). 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 (beta(3)-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.
Publisher: NATURE PUBLISHING GROUP
Keywords: TRANSCRIPTION FACTOR GATA-3; HUMAN BREAST-TUMORS; NERVOUS-SYSTEM; STEM-CELLS; GENE; EXPRESSION; CANCER; INITIATION; LINEAGE; THYMUS
Publisher's Version: https://doi.org/10.1038/ncb1530
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2007-02-01 12:00:00