Howlett A R, Bissell M J
Lawrence Berkeley Laboratory, University of California, Berkeley 94720.
Epithelial Cell Biol. 1993 Apr;2(2):79-89.
The morphogenesis and functional differentiation of mammary epithelium depends on signalling from systemic hormones and on cues from the local tissue microenvironment. With regard to the latter, regulatory cues are mainly provided by two subcompartments of the mesenchyme/stroma [fibroblastic and adipocyte] and the subjacent basement membrane. During embryogenesis, fibroblastic mesenchyme determines the sexual phenotype of the gland while adipocyte mesenchyme controls mammary-specific ductal morphogenesis. In the juvenile animal, adipocyte stroma continues to support ductal expansion while fibroblasts negatively regulate ductal outgrowth via interactions with the epithelium possibly involving TGF-beta mediated deposition of collagen I and chondroitin sulphate. In the adult, evidence from culture studies show that the signals required for the induction of tissue-specific differentiation during pregnancy and maintenance of function during lactation arise primarily from basement membrane. Beta-casein synthesis is induced in single mammary epithelial cells embedded within a basement membrane matrix via an integrin-dependent pathway. Further support for a critical role for basement membrane in the functional differentiation of the gland comes from studies in involution where degradative loss of basement membranes correlates with loss of functional activity in the epithelium. Thus the extracellular matrix in conjunction with certain cytokines plays a central role in coordinating mammary epithelial development. The findings discussed give further credence to a modal where mammary epithelium, together with certain elements of the subjacent microenvironment, form a dynamic and reciprocally interactive functional unit that regulates tissue specific gene expression in the mammary gland.
乳腺上皮的形态发生和功能分化取决于全身激素的信号传导以及局部组织微环境的线索。关于后者，调节线索主要由间充质/基质的两个亚区室[成纤维细胞和脂肪细胞]以及下方的基底膜提供。在胚胎发育过程中，成纤维细胞间充质决定腺体的性别表型，而脂肪细胞间充质控制乳腺特异性导管的形态发生。在幼年动物中，脂肪细胞基质继续支持导管扩张，而成纤维细胞通过与上皮细胞的相互作用对导管生长产生负调节，这可能涉及TGF-β介导的I型胶原蛋白和硫酸软骨素的沉积。在成年动物中，培养研究的证据表明，妊娠期间诱导组织特异性分化和哺乳期维持功能所需的信号主要来自基底膜。通过整合素依赖性途径，在嵌入基底膜基质中的单个乳腺上皮细胞中诱导β-酪蛋白合成。基底膜在腺体功能分化中起关键作用的进一步证据来自退化研究，其中基底膜的降解性丧失与上皮细胞功能活性的丧失相关。因此，细胞外基质与某些细胞因子共同在协调乳腺上皮发育中起核心作用。所讨论的研究结果进一步支持了一种模式，即乳腺上皮与下方微环境的某些成分一起形成一个动态且相互作用的功能单元，该单元调节乳腺中的组织特异性基因表达。
