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

Abstract	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 FGF-20 may be a critical element in oncogenesis induced by the Wnt signaling pathway.
Authors	Mario N Chamorro, Donald R Schwartz, Alin Vonica, Ali H Brivanlou, Kathleen R Cho, Harold E Varmus
Journal	The EMBO journal (EMBO J) Vol. 24 Issue 1 Pg. 73-84 (Jan 12 2005) ISSN: 0261-4189 [Print] England
PMID	15592430 (Publication Type: Journal Article)
Chemical References	CTNNB1 protein, Xenopus CTNNB1 protein, human CTNNB1 protein, mouse Cytoskeletal Proteins DKK1 protein, human Dkk1 protein, mouse FGF20 protein, human Fgf20 protein, mouse Intercellular Signaling Peptides and Proteins Proteins RNA, Small Interfering Trans-Activators Wnt Proteins Xenopus Proteins beta Catenin dkk1 protein, Xenopus Fibroblast Growth Factors
Topics	Adenocarcinoma (genetics, metabolism) Adenoma (genetics, metabolism) Animals Cell Line Cytoskeletal Proteins (metabolism) Epithelial Cells (cytology, physiology) Female Fibroblast Growth Factors (genetics, metabolism) Gene Expression Profiling Gene Expression Regulation Humans Intercellular Signaling Peptides and Proteins (metabolism) Intestinal Mucosa (physiology) Mice Neoplasms (genetics, metabolism) Oligonucleotide Array Sequence Analysis Ovarian Neoplasms (genetics, metabolism) Promoter Regions, Genetic Proteins (genetics, metabolism) RNA, Small Interfering (genetics, metabolism) Signal Transduction (physiology) Trans-Activators (metabolism) Transcription, Genetic Wnt Proteins Xenopus Proteins Xenopus laevis (embryology, genetics, metabolism) beta Catenin

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