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

ML Asselin-Labat, KD Sutherland, H Barker… - Nature cell …, 2007 - nature.com
ML Asselin-Labat, KD Sutherland, H Barker, R Thomas, M Shackleton, NC Forrest, L Hartley…
Nature cell biology, 2007nature.com
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 (β3-integrin) of luminal progenitor cells and their …
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 (β3-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.
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