Krupple-like factor 5 is essential for mammary gland development and tumorigenesis
Krupple-like factor 5 is essential for mammary gland development and tumorigenesis
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Krupple 样因子 5 对于乳腺发育和肿瘤发生至关重要。
DOI：
10.1002/path.5153
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发表时间：
2018-12-01
影响因子：
7.3
通讯作者：
Chen, Ceshi
中科院分区：
文献类型：
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作者：
Liu, Rong;Shi, Peiguo;Chen, Ceshi
Krupple-like factor 5（KLF 5）是胚胎和多个器官（如肺和肠）发育所必需的。KLF 5在包括乳腺癌在内的几种癌中起促增殖和致癌作用。然而，其在正常乳腺发育和肿瘤发生中的作用尚未在体内阐明。在这项研究中，我们使用了乳腺特异性Klf 5条件性敲除小鼠交配Klf 5-LoxP和MMTV-Cre小鼠。Klf 5的基因切除抑制乳腺导管伸长和小叶泡形成。Klf 5缺陷抑制乳腺上皮细胞增殖、存活和干细胞维持。Klf 5至少部分地通过直接促进Slug的转录来促进乳腺干性。最后，Klf 5耗尽抑制PyMT诱导的乳腺肿瘤细胞干细胞性、肿瘤起始和体内生长。Slug也在体内介导Klf 5的这些功能。版权所有（c）2018大不列颠和爱尔兰病理学会。由John Wiley & Sons有限公司出版
Krupple-like factor 5 (KLF5) is required for the development of the embryo and multiple organs, such as the lung and intestine. KLF5 plays a pro-proliferative and oncogenic role in several carcinomas, including breast cancer. However, its role in normal mammary gland development and oncogenesis has not been elucidated in vivo. In this study, we used mammary gland-specific Klf5 conditional knockout mice derived by mating Klf5-LoxP and MMTV-Cre mice. The genetic ablation of Klf5 suppresses mammary gland ductal elongation and lobuloalveolar formation. Klf5 deficiency inhibits mammary epithelial cell proliferation, survival, and stem cell maintenance. Klf5 promotes mammary stemness, at least partially, by directly promoting the transcription of Slug. Finally, Klf5 depletion suppressed PyMT-induced mammary gland tumor cell stemness, tumor initiation, and growth in vivo. Slug also mediated these functions of Klf5 in vivo. Copyright (c) 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.