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    Nat Cell Biol. 2007 Feb;9(2):201-9. Epub 2006 Dec 24.

    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.

    Source

    VBCRC Laboratory, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.

    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.

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    PMID:
    17187062
    [PubMed - indexed for MEDLINE]

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