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乳腺发育与癌症中细胞命运的调控机制

Mechanisms of Regulation of Cell Fate in Breast Development and Cancer.

作者信息

Van Keymeulen Alexandra

机构信息

Laboratory of Stem Cells and Cancer (LSCC), Université Libre de Bruxelles (ULB), Brussels, Belgium.

出版信息

Adv Exp Med Biol. 2025;1464:167-184. doi: 10.1007/978-3-031-70875-6_10.

Abstract

This chapter focuses on the mechanisms of regulation of cell fate in breast development, occurring mainly after birth, as well as in breast cancer. First, we will review how the microenvironment of the breast, as well as external cues, plays a crucial role in mammary gland cell specification and will describe how it has been shown to reprogram non-mammary cells into mammary epithelial cells. Then we will focus on the transcription factors and master regulators which have been established to be determinant for basal (BC) and luminal cell (LC) identity, and will describe the experiments of ectopic expression or loss of function of these transcription factors which demonstrated that they were crucial for cell fate. We will also discuss how master regulators are involved in the fate choice of LCs between estrogen receptor (ER)-positive cells and ER- cells, which will give rise to alveolar cells upon pregnancy and lactation. We will describe how oncogene expression induces reprogramming and change of fate of mammary epithelial cells before tumor appearance, which could be an essential step in tumorigenesis. Finally, we will describe the involvement of master regulators of mammary epithelial cells in breast cancer.

摘要

本章重点关注出生后主要发生的乳腺发育以及乳腺癌中细胞命运调控的机制。首先,我们将回顾乳腺的微环境以及外部信号如何在乳腺细胞特化中发挥关键作用,并描述如何已证明其能将非乳腺细胞重编程为乳腺上皮细胞。然后,我们将聚焦于已确定对基底细胞(BC)和腔面细胞(LC)身份起决定性作用的转录因子和主要调节因子,并描述这些转录因子的异位表达或功能丧失实验,这些实验表明它们对细胞命运至关重要。我们还将讨论主要调节因子如何参与腔面细胞在雌激素受体(ER)阳性细胞和ER阴性细胞之间的命运选择,这两种细胞在怀孕和哺乳时会分别产生肺泡细胞。我们将描述癌基因表达如何在肿瘤出现前诱导乳腺上皮细胞的重编程和命运改变,这可能是肿瘤发生的一个关键步骤。最后,我们将描述乳腺上皮细胞的主要调节因子在乳腺癌中的作用。

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