Figure 2.

Microarray transcript profiling and pathway analysis of TGF-β1+EGF-impacted genes in HaCaT II-4 keratinocytes. Focused microarrays of dual growth factor-stimulated HaCaT II-4 cells revealed the increased expression of mRNAs encoding proteins involved in angiogenesis, stromal invasion, and control of pericellular proteolysis. PAI-1 transcripts were the most highly upregulated (>168-fold), induced early (within 6 hours) of stimulation and prior to the onset of colony dispersal. Ingenuity Pathway clustergram mapping describes potential functional interactions among the complement of induced genes. Pathway analyses of many of these genes (see also Table 1) indicate that several including uPA, uPAR, SERPINE1, and the MMPs are TGF-β1 targets and encode key elements in the integrative proteolytic cascades that regulate focalized stromal degradation and tumor invasion.