Macias Hector, Hinck Lindsay
Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, CA, USA.
Wiley Interdiscip Rev Dev Biol. 2012 Jul-Aug;1(4):533-57. doi: 10.1002/wdev.35.
The mammary gland develops through several distinct stages. The first transpires in the embryo as the ectoderm forms a mammary line that resolves into placodes. Regulated by epithelial–mesenchymal interactions, the placodes descend into the underlying mesenchyme and produce the rudimentary ductal structure of the gland present at birth. Subsequent stages of development—pubertal growth, pregnancy, lactation, and involution—occur postnatally under the regulation of hormones. Puberty initiates branching morphogenesis, which requires growth hormone (GH) and estrogen, as well as insulin-like growth factor 1 (IGF1), to create a ductal tree that fills the fat pad. Upon pregnancy, the combined actions of progesterone and prolactin generate alveoli, which secrete milk during lactation. Lack of demand for milk at weaning initiates the process of involution whereby the gland is remodeled back to its prepregnancy state. These processes require numerous signaling pathways that have distinct regulatory functions at different stages of gland development. Signaling pathways also regulate a specialized subpopulation of mammary stem cells that fuel the dramatic changes in the gland occurring with each pregnancy. Our knowledge of mammary gland development and mammary stem cell biology has significantly contributed to our understanding of breast cancer and has advanced the discovery of therapies to treat this disease.
乳腺发育历经几个不同阶段。第一个阶段发生在胚胎期，外胚层形成乳腺线，进而发展为乳腺原基。在上皮 - 间充质相互作用的调控下，乳腺原基向下深入到下方的间充质中，并产生出生时就已存在的乳腺基本导管结构。随后的发育阶段——青春期生长、怀孕、哺乳和退化——在出生后受激素调控发生。青春期启动分支形态发生，这需要生长激素（GH）、雌激素以及胰岛素样生长因子1（IGF1），以形成填充脂肪垫的导管树。怀孕时，孕酮和催乳素的共同作用产生腺泡，腺泡在哺乳期间分泌乳汁。断奶时对乳汁需求的缺乏启动退化过程，在此过程中乳腺会重塑回到怀孕前的状态。这些过程需要众多信号通路，这些信号通路在乳腺发育的不同阶段具有不同的调节功能。信号通路还调节乳腺干细胞的一个特殊亚群，这些干细胞推动每次怀孕时乳腺发生的巨大变化。我们对乳腺发育和乳腺干细胞生物学的了解极大地促进了我们对乳腺癌的认识，并推动了治疗该疾病疗法的发现。
