EXTRACELLULAR MATRIX-DEPENDENT TISSUE-SPECIFIC GENE-EXPRESSION IN MAMMARY EPITHELIAL-CELLS REQUIRES BOTH PHYSICAL AND BIOCHEMICAL SIGNAL-TRANSDUCTION
EXTRACELLULAR MATRIX-DEPENDENT TISSUE-SPECIFIC GENE-EXPRESSION IN MAMMARY EPITHELIAL-CELLS REQUIRES BOTH PHYSICAL AND BIOCHEMICAL SIGNAL-TRANSDUCTION
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DOI：
10.1073/pnas.91.26.12378
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发表时间：
1994-12-20
影响因子：
11.1
通讯作者：
BISSELL, MJ
中科院分区：
文献类型：
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作者：
ROSKELLEY, CD;DESPREZ, PY;BISSELL, MJ
细胞外基质（Extracellular matrix，ECM）对乳腺上皮细胞的生长和分化具有重要影响。利用小鼠乳腺上皮细胞的克隆群体，绝对需要一个外源性ECM的功能，我们开发了一种快速测定法来研究ECM的信号转导。定义了导致乳蛋白β-酪蛋白表达的细胞对基底膜覆盖层反应的两个组成部分。这种反应的第一个组成部分涉及细胞的变圆和聚集，这可以通过将细胞接种在非粘附性基质上来物理模拟。第二种成分本质上是生物化学的，它与β（1）整合素聚集和酪氨酸磷酸化增加有关。第二种成分以形态学独立的方式启动，但将这种生化信号正确翻译为功能反应需要细胞变圆和细胞聚集。因此，物理和生物化学信号转导事件有助于ECM依赖性调节小鼠乳腺上皮细胞中的组织特异性基因表达。
Extracellular matrix (ECM) profoundly influeuces 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.