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

Marie Liesse Asselin-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

doi:10.1038/ncb1530

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

Marie Liesse Asselin-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 journal › Article › peer-review

671 Scopus citations

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 language	English (US)
Pages (from-to)	201-209
Number of pages	9
Journal	Nature Cell Biology
Volume	9
Issue number	2
DOIs	https://doi.org/10.1038/ncb1530
State	Published - Feb 2007
Externally published	Yes

ASJC Scopus subject areas

Cell Biology

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10.1038/ncb1530

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@article{eeb339acdb2c4a5bbe81dbdf23d9a494,

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 (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.",

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

note = "Funding Information: We are grateful to S. Holroyd and K. Johnson for expert technical assistance, F. Vaillant, J. Adams and K. Lim for discussions, S. Mihajlovic for histology, F. Battye and K. Field for FACS support, K.-U. Wagner and L. Hennighausen for WAP–cre and MMTV–cre transgenic mice, J. Jonkers for K14–cre mice, and H. Clevers for Lef1 plasmid. G.J.L. and J.E.V. are Research Fellows of the National Health and Medical Research Council (NHMRC) of Australia. M.-L.A.-L. is supported by an INSERM/NHMRC Postdoctoral Fellowship. M.S. was supported by a NHMRC Medical Postgraduate Scholarship. This work was supported by the Victorian Breast Cancer Research Consortium (J.E.V and G.J.L).",

year = "2007",

month = feb,

doi = "10.1038/ncb1530",

language = "English (US)",

volume = "9",

pages = "201--209",

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T1 - Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation

AU - Asselin-Labat, Marie Liesse

AU - Sutherland, Kate D.

AU - Barker, Holly

AU - Thomas, Richard

AU - Shackleton, Mark

AU - Forrest, Natasha C.

AU - Hartley, Lynne

AU - Robb, Lorraine

AU - Grosveld, Frank G.

AU - van der Wees, Jacqueline

AU - Lindeman, Geoffrey J.

AU - Visvader, Jane E.

N1 - Funding Information: We are grateful to S. Holroyd and K. Johnson for expert technical assistance, F. Vaillant, J. Adams and K. Lim for discussions, S. Mihajlovic for histology, F. Battye and K. Field for FACS support, K.-U. Wagner and L. Hennighausen for WAP–cre and MMTV–cre transgenic mice, J. Jonkers for K14–cre mice, and H. Clevers for Lef1 plasmid. G.J.L. and J.E.V. are Research Fellows of the National Health and Medical Research Council (NHMRC) of Australia. M.-L.A.-L. is supported by an INSERM/NHMRC Postdoctoral Fellowship. M.S. was supported by a NHMRC Medical Postgraduate Scholarship. This work was supported by the Victorian Breast Cancer Research Consortium (J.E.V and G.J.L).

PY - 2007/2

Y1 - 2007/2

N2 - 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.

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

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