In vitro multipotent differentiation and barrier function of a human mammary epithelium

被引:25
|
作者
Marshall, Aaron M. [1 ]
Pai, Vaibhav P. [1 ]
Sartor, Maureen A. [2 ]
Horseman, Nelson D. [1 ]
机构
[1] Univ Cincinnati, Dept Mol & Cellular Physiol, Syst Biol & Physiol Program, Cincinnati, OH 45267 USA
[2] Univ Cincinnati, Dept Environm Hlth, Ctr Environm Genet, Cincinnati, OH 45267 USA
基金
美国国家卫生研究院;
关键词
Breast; Transepithelial electrical resistance; Tight junctions; Milk protein; MCF10A; Gene expression profile; Human; HORMONE-RELATED PROTEIN; HUMAN BREAST-CANCER; GLAND DEVELOPMENT; STEM-CELLS; MYOEPITHELIAL CELLS; EXPRESSION; MOUSE; MORPHOGENESIS; PROLACTIN; IDENTIFICATION;
D O I
10.1007/s00441-008-0719-0
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
As demonstrated by a variety of animal studies, barrier function in the mammary epithelium is essential for a fully functioning and differentiated gland. However, there is a paucity of information on barrier function in human mammary epithelium. Here, we have established characteristics of a polarizing differentiating model of human mammary epithelial cells capable of forming a high-resistance/low-conductance barrier in a predictable manner, viz., by using MCF10A cells on permeable membranes. Inulin flux decreased and transepithelial electrical resistance (TEER) increased over the course of several days after seeding MCF10A cells on permeable membranes. MCF10A cells exhibited multipotent phenotypic differentiation into layers expressing basal and lumenal markers when placed on permeable membranes, with at least two distinct cell phenotypes. A clonal subline of MCF10A, generated by culturing stem-like cells under non-adherent conditions, also generated a barrier-forming epithelial membrane with cells expressing markers of both basal and lumenal differentiation (CD10 and MUC1, respectively). Progressive changes associated with differentiation, including wholesale inhibition of cell-cycle genes and stimulation of cell and tissue morphogenic genes, were observed by gene expression profiling. Clustering and gene ontology categorization of significantly altered genes revealed a pattern of lumenal epithelial-cell-specific differentiation.
引用
收藏
页码:383 / 395
页数:13
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