转录因子EHF在哺乳期乳腺中高表达，但其在乳腺发育和肿瘤发生中的作用尚不完全清楚。利用 Ehf 缺失的小鼠模型，我们证明 Ehf 的缺失会损害妊娠后期的乳腺小叶肺泡分化，表现为乳基因和乳脂水平显着降低、分化的肺泡细胞减少以及肺泡祖细胞的积累。此外，Ehf 的缺失增加了乳腺类器官的增殖能力并减弱了催乳素诱导的肺泡分化。 Ehf 缺失还增加了 MMTV-PyMT 乳腺肿瘤模型中的肿瘤发生率，并增加了乳腺肿瘤类器官的增殖能力，而低 EHF 表达与 Luminal A 和基底人类乳腺癌中较高的肿瘤分级和较差的结果相关。总的来说，这些发现确立了 EHF 作为乳腺肺泡分化的非冗余调节剂和乳腺肿瘤发生的假定抑制因子。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

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.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.