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

Nightingale, R; Reehorst, CM; Vukelic, N; Papadopoulos, N; Liao, Y; Guleria, S; Bell, C; Vaillant, F; Paul, S; Luk, IY; Dhillon, AS; Jenkins, LJ; Morrow, RJ; Jackling, FC; Chand, AL; Chisanga, D; Chen, Y; Williams, DS; Anderson, RL; Ellis, S; Meikle, PJ; Shi, W; Visvader, JE; Pal, B; Mariadason, JM

Author(s): Nightingale, R; Reehorst, CM; Vukelic, N; Papadopoulos, N; Liao, Y; Guleria, S; Bell, C; Vaillant, F; Paul, S; Luk, IY; Dhillon, AS; Jenkins, LJ; Morrow, RJ; Jackling, FC; Chand, AL; Chisanga, D; Chen, Y; Williams, DS; Anderson, RL; Ellis, S; Meikle, PJ; Shi, W; Visvader, JE; Pal, B; Mariadason, JM;
Details: Publication Year 2024-08-05,Volume 59,Issue #15,Page 1988-2004.e11
Journal Title: Developmental Cell
Publication Type: Research article
Abstract: 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.
Publisher: Cell Press
Keywords: Animals; Female; *Cell Differentiation; Mice; *Mammary Glands, Animal/pathology/metabolism/growth & development/cytology; *Breast Neoplasms/pathology/genetics/metabolism; Humans; Carcinogenesis/pathology/metabolism/genetics; Cell Lineage; Transcription Factors/metabolism/genetics; Cell Proliferation; Alveolar Epithelial Cells/metabolism/pathology/cytology; Pregnancy; Lactation; Ehf; alveologenesis; breast cancer; breast tumorigenesis; mammary development; mammary gland; mouse; organoid; post-natal mammary development; transcription factor
Department(s): Laboratory Research
Publisher's Version: https://doi.org/10.1016/j.devcel.2024.04.022
Open Access at Publisher's Site: https://doi.org/10.1016/j.devcel.2024.04.022
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-09-19 02:59:44

Last Modified: 2024-09-19 03:00:01