Yarwood S J, Woodgett J R
Ontario Cancer Institute/Princess Margaret Hospital, Toronto, ON, Canada M5G 2M9.
Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4472-7. doi: 10.1073/pnas.081069098. Epub 2001 Apr 3.
The transcriptional response to epidermal growth factor (EGF) was examined in a cultured cell model of adhesion. Gene expression was monitored in human embryonic kidney cells (HEK293) after attachment of cells to the extracellular matrix (ECM) proteins, laminin, and fibronectin, by using complementary DNA microarrays printed with 1,718 individual human genes. Cluster analysis revealed that the influence of EGF on gene expression, either positive or negative, was largely independent of ECM composition. However, clusters of EGF-regulated genes were identified that were diagnostic of the type of ECM proteins to which cells were attached. In these clusters, attachment of cells to a laminin or fibronectin substrata specifically modified the direction of gene expression changes in response to EGF stimulation. For example, in HEK293 cells attached to fibronectin, EGF stimulated an increase in the expression of some genes; however, genes in the same group were nonresponsive or even suppressed in cells attached to laminin. Many of the genes regulated by EGF and ECM proteins in this manner are involved in ECM and cytoskeletal architecture, protein synthesis, and cell cycle control, indicating that cell responses to EGF stimulation can be dramatically affected by ECM composition.
在一种黏附培养细胞模型中研究了对表皮生长因子（EGF）的转录反应。通过使用印有1718个人类基因的互补DNA微阵列，在人胚胎肾细胞（HEK293）将细胞附着于细胞外基质（ECM）蛋白、层粘连蛋白和纤连蛋白后监测基因表达。聚类分析表明，EGF对基因表达的影响，无论是正向还是负向，在很大程度上独立于ECM组成。然而，鉴定出了受EGF调节的基因簇，这些基因簇可诊断细胞所附着的ECM蛋白类型。在这些基因簇中，细胞附着于层粘连蛋白或纤连蛋白基质会特异性地改变对EGF刺激的基因表达变化方向。例如，在附着于纤连蛋白的HEK293细胞中，EGF刺激了一些基因的表达增加；然而，同一组基因在附着于层粘连蛋白的细胞中无反应甚至被抑制。以这种方式受EGF和ECM蛋白调节的许多基因参与ECM和细胞骨架结构、蛋白质合成以及细胞周期控制，表明细胞对EGF刺激的反应会受到ECM组成的显著影响。
