Extracellular Matrix Dependent Gene Regulation in Mammary Epithelial Cells

Abstract

The dynamic and reciprocal interactions of cells with their extracellular tissue microenvironment has provided the basis for the hypothesis that external cues such as extracellular matrix (ECM) proteins, and in particular the basement membrane underlying the epithelial tissue, acts as a key regulator of many aspects of cell behaviour (Bissell et al., 1982). Ample evidence shows that controlled cellular interactions with the basement membrane are essential for the development and maintenance of the differentiated phenotype in many cell types (Stocker et al., 1990; Wicha et al., 1982; Lee et al., 1984; Durban et al., 1985; Li et al., 1987; Blum et al., 1987; Schmidhauser et al., 1990; Taub et al., 1990; Streuli and Bissell, 1990; Wang et al., 1990; Takahashi and Nogawa, 1991; Montesano et al., 1991; Peterson et al., 1992). Such signals control at least in part growth, morphology, and biochemical differentiation. A number of systems provide evidence for the requirement of ECM-derived signals to regulate their differentiation programmes. One such system is the mammary epithelial cell in which the expression of milk proteins is tightly controlled by the interactions of the alveolar cells with their underlying basement membrane (Streuli, 1993). In particular the regulation of the milk proteins β-casein (Barcellos-Hoff et al., 1989; Schmidhauser et al., 1990) and whey acidic protein (WAP; Chen and Bissell, 1989) have been well-characterized.