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

Marie-Liesse Labat, Kate D. Sutherland, Holly Barker, Richard Thomas, Mark Shackleton, Natasha C. Forrest, Lynne Hartley, Lorraine Robb, Frank G. Grosveld, Jacqueline van der Wees, Geoffrey J. Lindeman, Jane E. Visvader

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)201-209
Number of pages9
JournalNature Cell Biology
Volume9
Issue number2
DOIs
StatePublished - Feb 1 2007
Externally publishedYes

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Human Mammary Glands
Morphogenesis
Cell Differentiation
Stem Cells
Transcription Factor 3
Integrins
Carcinogenesis
Breast
Embryonic Structures
Breast Neoplasms
Population

ASJC Scopus subject areas

  • Cell Biology

Cite this

Labat, M-L., Sutherland, K. D., Barker, H., Thomas, R., Shackleton, M., Forrest, N. C., ... Visvader, J. E. (2007). Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation. Nature Cell Biology, 9(2), 201-209. https://doi.org/10.1038/ncb1530

Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation. / Labat, Marie-Liesse; Sutherland, Kate D.; Barker, Holly; Thomas, Richard; Shackleton, Mark; Forrest, Natasha C.; Hartley, Lynne; Robb, Lorraine; Grosveld, Frank G.; van der Wees, Jacqueline; Lindeman, Geoffrey J.; Visvader, Jane E.

In: Nature Cell Biology, Vol. 9, No. 2, 01.02.2007, p. 201-209.

Research output: Contribution to journalArticle

Labat, M-L, Sutherland, KD, Barker, H, Thomas, R, Shackleton, M, Forrest, NC, Hartley, L, Robb, L, Grosveld, FG, van der Wees, J, Lindeman, GJ & Visvader, JE 2007, 'Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation', Nature Cell Biology, vol. 9, no. 2, pp. 201-209. https://doi.org/10.1038/ncb1530
Labat, Marie-Liesse ; Sutherland, Kate D. ; Barker, Holly ; Thomas, Richard ; Shackleton, Mark ; Forrest, Natasha C. ; Hartley, Lynne ; Robb, Lorraine ; Grosveld, Frank G. ; van der Wees, Jacqueline ; Lindeman, Geoffrey J. ; Visvader, Jane E. / Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation. In: Nature Cell Biology. 2007 ; Vol. 9, No. 2. pp. 201-209.
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