Fig. 6.

Model for PEA3-dependent regulation of FGF-10 in normal and malignant cells. In a non-malignant epithelial cell expressing FGFR1B or FGFR2B, FGF-10 secreted from a nearby cell can act in a paracrine fashion to activate its receptors and upregulate target genes, including Pea3. PEA3 protein can then bind to specific consensus sequences in the Fgf-10 promoter, blocking transcription. In the cancer cells we used, PEA3 protein was unstable, meaning that it could not bind to the Fgf-10 promoter. As a result, FGF-10 was expressed and able to stimulate its receptors in an autocrine fashion, thus providing the cancer cell with a strong growth-promoting signal.