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FGF‐20 and DKK1 are transcriptional targets of β‐catenin and FGF‐20 is implicated in cancer and development
Author(s) -
Chamorro Mario N,
Schwartz Donald R,
Vonica Alin,
Brivanlou Ali H,
Cho Kathleen R,
Varmus Harold E
Publication year - 2005
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600460
Subject(s) - biology , wnt signaling pathway , dkk1 , beta catenin , microbiology and biotechnology , carcinogenesis , catenin , cancer research , signal transduction , gene , genetics
β‐catenin is the major effector of the canonical Wnt signaling pathway. Mutations in components of the pathway that stabilize β‐catenin result in augmented gene transcription and play a major role in many human cancers. We employed microarrays to identify transcriptional targets of deregulated β‐catenin in a human epithelial cell line (293) engineered to produce mutant β‐catenin and in ovarian endometrioid adenocarcinomas characterized with respect to mutations affecting the Wnt/β‐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 β‐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 β‐catenin, implying that FGF‐20 may be a critical element in oncogenesis induced by the Wnt signaling pathway.