Extracellular matrix composition determines the transcriptional response to epidermal growth factor receptor activation.
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.
Yarwood
S J
SJ
Ontario Cancer Institute/Princess Margaret Hospital, Toronto, ON, Canada M5G 2M9. syarwood@udcf.gla.ac.uk
Woodgett
J R
JR
D015153:Blotting, Western; D002460:Cell Line; D016000:Cluster Analysis; D066246:ErbB Receptors / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D011233:Precipitin Tests; D014158:Transcription, Genetic
D016326:Extracellular Matrix Proteins; D066246:ErbB Receptors