Pujuguet P, Radisky D, Levy D, Lacza C, Bissell M J
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
J Cell Biochem. 2001;83(4):660-70. doi: 10.1002/jcb.1260.
Many aspects of cellular behavior are defined by the content of information provided by association of the extracellular matrix (ECM) and with cell membrane receptors. When cultured in the presence of laminin-containing ECM and prolactin (Prl), normal mammary epithelial cells express the milk protein beta-casein. We have previously found that the minimal ECM- and Prl-responsive enhancer element BCE-1 was only active when stably integrated into chromatin, and that trichostatin A (TSA), a reagent that leads to alterations in chromatin structure, was able to activate the integrated enhancer element. We now show that endogenous beta-casein gene, which is controlled by a genetic assembly that is highly similar to that of BCE-1 and which is also activated by incubation in ECM and Prl, is instead inhibited by TSA. We provide evidence that the differing response of beta-casein and BCE-1 to TSA is neither due to an unusual effect of TSA on mammary epithelial cells, nor to secondary consequences from the expression of a separate gene, nor to a particular property of the BCE-1 construct. As a component of this investigation, we also showed that ECM mediated rapid histone deacetylation in mammary epithelial cells. These results are discussed in combination with previous work showing that TSA mediates the differentiation of many types of cancer cells but inhibits differentiation of some nonmalignant cell types.
细胞行为的许多方面是由细胞外基质（ECM）与细胞膜受体结合所提供的信息内容来定义的。当在含有层粘连蛋白的ECM和催乳素（Prl）存在的情况下培养时，正常乳腺上皮细胞会表达乳蛋白β-酪蛋白。我们之前发现，最小的ECM和Prl反应增强子元件BCE-1只有在稳定整合到染色质中时才具有活性，并且曲古抑菌素A（TSA），一种能导致染色质结构改变的试剂，能够激活整合的增强子元件。我们现在表明，内源性β-酪蛋白基因，其受与BCE-1高度相似的基因组装控制，并且在ECM和Prl中孵育时也被激活，但却被TSA抑制。我们提供的证据表明，β-酪蛋白和BCE-1对TSA的不同反应既不是由于TSA对乳腺上皮细胞的异常作用，也不是由于单独基因表达的次生后果，也不是由于BCE-1构建体的特殊性质。作为这项研究的一部分，我们还表明ECM介导了乳腺上皮细胞中的快速组蛋白去乙酰化。这些结果与之前的工作结合起来进行讨论，之前的工作表明TSA介导了许多类型癌细胞的分化，但抑制了一些非恶性细胞类型的分化。
