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FGF-20 and DKK1 Are Transcriptional Targets of Beta-Catenin and FGF-20 Is Implicated in Cancer and Development

FGF-20 and DKK1 Are Transcriptional Targets of Beta-Catenin and FGF-20 Is Implicated in Cancer and Development

Mario N Chamorro, Donald R Schwartz, Alin Vonica, Ali H Brivanlou, Kathleen R Cho, Harold E Varmus

EMBO J. 2005 Jan 12;24(1):73-84.

PMID: 15592430

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248813	FGF-20 human			Price

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