Experimental mammary epithelial morphogenesis in an in vivo model: Evidence for distinct cellular progenitors of the ductal and lobular phenotype
Experimental mammary epithelial morphogenesis in an in vivo model: Evidence for distinct cellular progenitors of the ductal and lobular phenotype
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DOI：
10.1007/bf01806075
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发表时间：
1996-01-01
影响因子：
3.8
通讯作者：
Smith, GH
中科院分区：
文献类型：
--
作者：
Smith, GH
一种体内移植系统已被用于评估特定小鼠乳腺上皮细胞群的发育能力。具体而言，通过这一程序已鉴定出发育潜能明显受限的小鼠乳腺上皮细胞。通过旨在确定在有限稀释条件下基底小叶和导管表型是否能独立发育的实验，已鉴定出两种不同的上皮细胞祖细胞。关于这些独立的上皮祖细胞必定存在的预测是基于在同基因小鼠去除上皮的乳腺脂肪垫中进行的移植实验结果，这些实验使用了来自两种不同转基因小鼠模型的乳腺上皮。此处呈现的结果表明以下几点：1）在未成熟的处女雌性小鼠的乳腺上皮细胞中，小叶（即分泌性）祖细胞作为不同的实体存在；2）同样，导管上皮祖细胞存在于同一细胞群中；3）小叶祖细胞数量更多，尽管两种细胞群都极少；4）正如所预期的，一些接种物会产生同时发育出小叶和导管表型的生长物——尚不清楚这是否表明两种上皮祖细胞之间存在协同作用，还是意味着存在第三种能够产生定向分化为导管和小叶的子代细胞的祖细胞类型；5）这些发现对于旨在测试已知和假定的乳腺癌基因和肿瘤抑制基因影响的实验设计具有重要意义，这些实验所采用的技术包括体外细胞转化，随后进行体内培养和评估。
An in vivo transplantation system has been used to evaluate the developmental capacities of specific mouse mammary epithelial cell populations. Specifically, mouse mammary epithelial cells with distinctly limited developmental potentials have been identified using this procedure. Two distinct epithelial cell progenitors have been identified by experiments designed to determine whether basal lobular and ductal phenotypes could develop independently under conditions imposed by a limiting dilution. The prediction that these separate epithelial progenitors must exist was based upon the results from transplantation experiments carried out in epithelium-divested mammary fat pads of syngeneic mice with mammary epithelium from two different transgenic mouse models. The results presented here demonstrate the following points: 1) lobular, i.e. secretory, progenitor cells are present as distinct entities among the mammary epithelial cells found in immature virgin female mice; 2) similarly, ductal epithelial progenitors are present within the same population; 3) lobular progenitors are present in greater numbers, although both cell populations are extremely small; 4) as expected, some inocula produce outgrowths with simultaneous development of both lobular and ductal phenotypes - it is not known whether this indicates cooperative interaction between the two epithelial progenitors or signals the presence of a third progenitor type capable of producing both ductular and lobular committed daughters; 5) these findings have important consequences in the design of experiments aimed at testing the effects of known and putative mammary oncogenes and tumor suppressor genes, using techniques which include cellular transformation in vitro followed by in vivo cultivation and evaluation.