Letter abstract
Nature Cell Biology 9, 201 - 209 (2006)
Published online: 24 December 2006 | doi:10.1038/ncb1530
Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation
Marie-Liesse Asselin-Labat1,8, Kate D. Sutherland1,6,8, Holly Barker1,2, Richard Thomas1, Mark Shackleton1,2,7, Natasha C. Forrest1, Lynne Hartley3, Lorraine Robb3, Frank G. Grosveld4, Jacqueline van der Wees4, Geoffrey J. Lindeman1,5 & Jane E. Visvader1
The transcription factor Gata-3 is a defining marker of the 'luminal' subtypes of breast cancer1, 2, 3, 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 (
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.
- VBCRC Laboratory, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
- Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
- Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
- Department of Cell Biology, Erasmus Medical Center, 3000 DR, Rotterdam, The Netherlands.
- Department of Medical Oncology, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
- Current address: The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands.
- Current address: Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
- These authors contributed equally to this work.
Correspondence to: Jane E. Visvader1 e-mail: visvader@wehi.edu.au
Correspondence to: Geoffrey J. Lindeman1,5 e-mail: lindeman@wehi.edu.au
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