FGF-20 and DKK1 are transcriptional targets of β-catenin and FGF-20 is implicated in cancer and development

beta-catenin is the major effector of the canonical Wnt signaling pathway. Mutations in components of the pathway that stabilize beta- catenin result in augmented gene transcription and play a major role in many human cancers. We employed microarrays to identify transcriptional targets of deregulated beta-catenin in a human epithelial cell line ( 293) engineered to produce mutant beta-catenin and in ovarian endometrioid adenocarcinomas characterized with respect to mutations affecting the Wnt/beta-catenin pathway. Two genes strongly induced in both systems - FGF20 and DKK1 - were studied in detail. Elevated levels of FGF20 RNA were also observed in adenomas from mice carrying the Apc(Min) allele. Both XFGF20 and Xdkk- 1 are expressed early in Xenopus embryogenesis under the control of the Wnt signaling pathway. Furthermore, FGF20 and DKK1 appear to be direct targets for beta-catenin/ TCF transcriptional regulation via LEF/ TCF- binding sites. Finally, by using small inhibitory RNAs specific for FGF20, we show that continued expression of FGF20 is necessary for maintenance of the anchorage- independent growth state in RK3E cells transformed by beta-catenin, implying that FGF20 may be a critical element in oncogenesis induced by the Wnt signaling pathway.