Deugnier M A, Moiseyeva E P, Thiery J P, Glukhova M
Laboratoire de Physiopathologie du Développement, CNRS URA 1337, Ecole Normale Supérieure, Paris, France.
Dev Dyn. 1995 Oct;204(2):107-17. doi: 10.1002/aja.1002040202.
The most important portion of the mammary gland development occurs postnatally, with distinct periods of intensive morphogenesis taking place between birth and puberty and during pregnancy and lactation. To characterize the differentiation process of mammary myoepithelial cells, we have studied the expression patterns of several smooth muscle phenotypic markers, including contractile proteins, alpha-smooth muscle-actin (alpha-SM-actin), smooth muscle myosin heavy chains (SM-MHC), and calponin; components of cell-extracellular matrix adherens junctions, phosphoglucomutase-related protein (PGM), vinculin variants, integrin subunits; and laminin variant chains in the developing rat mammary gland using immunofluorescence microscopy. alpha-SM-actin- and SM-MHC-positive cells were found first in newborn animals, while calponin, PGM and alpha1 integrin subunit began to be expressed in prepubertal animals (1.5 weeks). Vinculin, beta1 and alpha3 integrin subunits were largely confined to the basal cell layer at all developmental stages examined with greater staining starting at 1.5 weeks. Meta-vinculin was identified only in myoepithelial cells of the lactating gland. gamma1 laminin chain was present in the mammary gland basement membrane throughout development, while the beta2 chain was revealed in 3-week-old animals and accumulated later in postpubertal animals (7 weeks). Similarly, beta2 laminin chain was absent from the forming alveoli basement membrane in pregnant rats and started to accumulate in the lactating gland. In addition to temporal changes, we have observed spatial differences in the distribution of the phenotypic markers. Both in pre- and in postpubertal animals, alpha-SM-actin- and SM-MHC-positive cells of the growing ductal ends contained low amounts if any of calponin, PGM, and beta2 laminin chain. We conclude that during postnatal development, mammary myoepithelial cells progressively acquire a differentiated phenotype as revealed by the expression of various smooth muscle markers. Maturation of the myoepithelial cells is accompanied by upregulation of the smooth muscle integrin expression followed by accumulation of beta2-containing laminin variant. Thus, changes in adhesion system parallel with the myoepithelial cell differentiation.
乳腺发育最重要的部分发生在出生后，在出生至青春期以及怀孕和哺乳期间会出现不同的密集形态发生期。为了表征乳腺肌上皮细胞的分化过程，我们研究了几种平滑肌表型标志物的表达模式，包括收缩蛋白、α-平滑肌肌动蛋白（α-SM-肌动蛋白）、平滑肌肌球蛋白重链（SM-MHC）和钙调蛋白；细胞-细胞外基质黏附连接的成分、磷酸葡萄糖变位酶相关蛋白（PGM）、纽蛋白变体、整合素亚基；以及使用免疫荧光显微镜观察发育中的大鼠乳腺中的层粘连蛋白变体链。α-SM-肌动蛋白和SM-MHC阳性细胞首先在新生动物中发现，而钙调蛋白、PGM和α1整合素亚基在青春期前动物（1.5周）开始表达。纽蛋白、β1和α3整合素亚基在所有检查的发育阶段主要局限于基底细胞层，从1.5周开始染色增强。间纽蛋白仅在泌乳期乳腺的肌上皮细胞中被鉴定出来。γ1层粘连蛋白链在整个发育过程中存在于乳腺基底膜中，而β2链在3周龄动物中被发现，并在青春期后动物（7周）中积累。同样，β2层粘连蛋白链在怀孕大鼠形成的肺泡基底膜中不存在，并开始在泌乳期乳腺中积累。除了时间变化外，我们还观察到表型标志物分布的空间差异。在青春期前和青春期后动物中，生长导管末端的α-SM-肌动蛋白和SM-MHC阳性细胞中钙调蛋白、PGM和β2层粘连蛋白链的含量都很低（如果有的话）。我们得出结论，在出生后发育过程中，乳腺肌上皮细胞通过各种平滑肌标志物的表达逐渐获得分化表型。肌上皮细胞的成熟伴随着平滑肌整合素表达的上调，随后是含β2的层粘连蛋白变体的积累。因此，黏附系统的变化与肌上皮细胞分化平行。
