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PMID: 15592430 Published · ppublish English Journal Article

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

The EMBO journal ·Vol. 24 ·No. 1 ·2005-01-12 ·Pages 73-84

Chamorro MN, Schwartz DR, Vonica A, Brivanlou AH, Cho KR, Varmus HE

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.

MeSH Terms
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
Chemicals
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
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Chamorro Mario N
Cancer Biology and Genetics Program, Sloan-Kettering Institute, Varmus Laboratory, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Schwartz Donald R
Vonica Alin
Brivanlou Ali H
Cho Kathleen R
Varmus Harold E
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7600460
Published
2005-01-12
Epub
2004-00-09
Pages
73-84
Language
English
Region
England
NLM ID
8208664
PMCID
PMC544900
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.emboj.7600460 PMC Full Text View journal details
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