Article
- The EMBO Journal (2005) 24, 73 - 84
- doi:10.1038/sj.emboj.7600460
Published online: 9 December 2004
Subject Categories:
FGF-20 and DKK1 are transcriptional targets of 
-catenin and FGF-20 is implicated in cancer and development
Mario N Chamorro1,4, Donald R Schwartz2,a, Alin Vonica3,a, Ali H Brivanlou3, Kathleen R Cho2 and Harold E Varmus1
- Cancer Biology and Genetics Program, Sloan-Kettering Institute, Varmus Laboratory, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
- Department of Pathology, The University of Michigan Medical School, Ann Arbor, MI, USA
- The Laboratory of Vertebrate Embryology, The Rockefeller University, New York, NY, USA
- Cell Biology Program, Cornell University, Weill Graduate School of Medical Sciences, New York, NY, USA
Correspondence to:
Harold E Varmus, Cancer Biology and Genetics Program, Sloan-Kettering Institute, Varmus Laboratory-RRL717, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 62, New York, NY 10021, USA. Tel.: +1 212 639 6561; Fax: +1 212 717 3125; E-mail: varmus@mskcc.org
aThese authors contributed equally to this work
Received 4 June 2004; Accepted 6 October 2004
Abstract
-catenin is the major effector of the canonical Wnt signaling pathway. Mutations in components of the pathway that stabilize -catenin result in augmented gene transcription and play a major role in many human cancers. We employed microarrays to identify transcriptional targets of deregulated -catenin in a human epithelial cell line (293) engineered to produce mutant -catenin and in ovarian endometrioid adenocarcinomas characterized with respect to mutations affecting the Wnt/-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 ApcMinallele. 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 -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 -catenin, implying that FGF-20 may be a critical element in oncogenesis induced by the Wnt signaling pathway.
Keywords:
- -catenin,
- DKK1,
- FGF-20,
- Wnt signaling,
- Xenopus laevis
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