During epithelial-mesenchymal transition (EMT), epithelial cells are converted into isolated motile and invasive mesenchymal cells. In model systems, EMT is induced most often by the activation of
tyrosine kinase receptors through signaling pathways involving translational and post-translational regulation. In this study, we have used the NBT-II bladder
carcinoma cell system to investigate in vitro
Fibroblast Growth Factor-1 (FGF-1)-induced EMT. Transcriptome analyses were performed on NBT-II cells stimulated for 2, 6, 24, and 48 h with
FGF-1. As some phenotypic changes occurred around 6 h post-stimulation, a supervised analysis was designed to identify transcript variations across defined time-periods. Our results clearly indicate that immediately after
FGF-1 stimulation a set of genes assigned to transcriptional regulation (e.g., jun-B and v-ets) and to EMT induction (e.g., Notch 1) is transiently up-regulated. A set of genes involved in proteolytic systems (e.g.,
MMP-13 and uPAR) is immediately up-regulated but subsequently maintained throughout
FGF-1 stimulation. Then follows a second wave of gene expression that includes a strong but transient up-regulation of
ephrin B1 and
arginase I. Finally, a third group of genes is stably modulated over 48 h which consists primarily of down-regulated genes specifically associated with the EMT-based loss of the epithelial phenotype and maintenance of the mesenchymal and invasive phenotype of
carcinoma cells. Using genome-wide oligoarray technology, we have identified novel expressions of immediate, immediate-early and later EMT
biomarkers that are specifically activated downstream of the FGF/FGFR pathway and which might be significant prognostic factors for
tumor progression of
carcinoma.