Ehf controls mammary alveolar lineage differentiation and is a putative suppressor of breast tumorigenesis.

Autor:	Nightingale R; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, La Trobe University, Bundoora, VIC 3086, Australia., Reehorst CM; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, La Trobe University, Bundoora, VIC 3086, Australia., Vukelic N; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, La Trobe University, Bundoora, VIC 3086, Australia., Papadopoulos N; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, La Trobe University, Bundoora, VIC 3086, Australia., Liao Y; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, La Trobe University, Bundoora, VIC 3086, Australia., Guleria S; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, La Trobe University, Bundoora, VIC 3086, Australia., Bell C; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, La Trobe University, Bundoora, VIC 3086, Australia., Vaillant F; Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia., Paul S; Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia; Baker Department of Cardiovascular Research Translation and Implementation, La Trobe University, Bundoora, VIC 3086, Australia., Luk IY; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, La Trobe University, Bundoora, VIC 3086, Australia., Dhillon AS; The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, VIC 3220, Australia., Jenkins LJ; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, La Trobe University, Bundoora, VIC 3086, Australia., Morrow RJ; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, La Trobe University, Bundoora, VIC 3086, Australia., Jackling FC; Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia., Chand AL; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, La Trobe University, Bundoora, VIC 3086, Australia., Chisanga D; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, La Trobe University, Bundoora, VIC 3086, Australia., Chen Y; Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia; Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia., Williams DS; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, La Trobe University, Bundoora, VIC 3086, Australia; Department of Pathology, Austin Health, Heidelberg, VIC 3084, Australia., Anderson RL; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, La Trobe University, Bundoora, VIC 3086, Australia; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia., Ellis S; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, La Trobe University, Bundoora, VIC 3086, Australia., Meikle PJ; Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia; Baker Department of Cardiovascular Research Translation and Implementation, La Trobe University, Bundoora, VIC 3086, Australia., Shi W; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, La Trobe University, Bundoora, VIC 3086, Australia., Visvader JE; Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia., Pal B; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, La Trobe University, Bundoora, VIC 3086, Australia. Electronic address: bhupinder.pal@onjcri.org.au., Mariadason JM; Olivia Newton-John Cancer Research Institute, Heidelberg, VIC 3084, Australia; School of Cancer Medicine, La Trobe University, Bundoora, VIC 3086, Australia; Department of Medicine, University of Melbourne, Parkville, VIC 3052, Australia. Electronic address: john.mariadason@onjcri.org.au.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2024 Aug 05; Vol. 59 (15), pp. 1988-2004.e11. Date of Electronic Publication: 2024 May 22.
DOI:	10.1016/j.devcel.2024.04.022
Abstrakt:	The transcription factor EHF is highly expressed in the lactating mammary gland, but its role in mammary development and tumorigenesis is not fully understood. Utilizing a mouse model of Ehf deletion, herein, we demonstrate that loss of Ehf impairs mammary lobuloalveolar differentiation at late pregnancy, indicated by significantly reduced levels of milk genes and milk lipids, fewer differentiated alveolar cells, and an accumulation of alveolar progenitor cells. Further, deletion of Ehf increased proliferative capacity and attenuated prolactin-induced alveolar differentiation in mammary organoids. Ehf deletion also increased tumor incidence in the MMTV-PyMT mammary tumor model and increased the proliferative capacity of mammary tumor organoids, while low EHF expression was associated with higher tumor grade and poorer outcome in luminal A and basal human breast cancers. Collectively, these findings establish EHF as a non-redundant regulator of mammary alveolar differentiation and a putative suppressor of mammary tumorigenesis. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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