Roskelley C D, Desprez P Y, Bissell M J
Life Sciences Division, Lawrence Berkeley Laboratory, Berkeley, CA 94720.
Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12378-82. doi: 10.1073/pnas.91.26.12378.
Extracellular matrix (ECM) profoundly influences the growth and differentiation of the mammary gland epithelium, both in culture and in vivo. Utilizing a clonal population of mouse mammary epithelial cells that absolutely requires an exogenous ECM for function, we developed a rapid assay to study signal transduction by ECM. Two components of the cellular response to a basement membrane overlay that result in the expression of the milk protein beta-casein were defined. The first component of this response involves a rounding and clustering of the cells that can be physically mimicked by plating the cells on a nonadhesive substratum. The second component is biochemical in nature, and it is associated with beta 1 integrin clustering and increased tyrosine phosphorylation. The second component is initiated in a morphology-independent manner, but the proper translation of this biochemical signal into a functional response requires cell rounding and cell clustering. Thus, physical and biochemical signal transduction events contribute to the ECM-dependent regulation of tissue-specific gene expression in mouse mammary epithelial cells.
细胞外基质（ECM）在体外培养和体内环境中都对乳腺上皮细胞的生长和分化有着深远影响。利用一群克隆的小鼠乳腺上皮细胞，其功能绝对依赖于外源性细胞外基质，我们开发了一种快速检测方法来研究细胞外基质的信号转导。确定了细胞对基底膜覆盖物产生反应并导致乳蛋白β-酪蛋白表达的两个组成部分。这种反应的第一个组成部分涉及细胞变圆和聚集，这可以通过将细胞接种在非粘性基质上进行物理模拟。第二个组成部分本质上是生化性质的，它与β1整合素聚集和酪氨酸磷酸化增加有关。第二个组成部分以与形态无关的方式启动，但这种生化信号正确转化为功能性反应需要细胞变圆和细胞聚集。因此，物理和生化信号转导事件有助于细胞外基质对小鼠乳腺上皮细胞中组织特异性基因表达的依赖性调节。
