FGF-20 and DKK1 are transcriptional targets of β-catenin and FGF-20 is implicated in cancer and development Journal Article
| Authors: | Chamorro, M. N.; Schwartz, D. R.; Vonica, A.; Brivanlou, A. H.; Cho, K. R.; Varmus, H. E. |
| Article Title: | FGF-20 and DKK1 are transcriptional targets of β-catenin and FGF-20 is implicated in cancer and development |
| Abstract: | 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 ApcMin 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. |
| Keywords: | signal transduction; controlled study; human tissue; intercellular signaling peptides and proteins; unclassified drug; dna binding protein; gene mutation; human cell; nonhuman; endometrioid carcinoma; mutant protein; neoplasms; adenocarcinoma; ovarian neoplasms; proteins; animal cell; mouse; animals; mice; animal tissue; gene; proto oncogene; gene expression; gene expression profiling; cell line; small interfering rna; rna, small interfering; embryo development; genetic transcription; transcription, genetic; carcinogenesis; rna; gene expression regulation; tumor suppressor gene; adenoma; genetic engineering; oligonucleotide array sequence analysis; cell transformation; rat; epithelium cell; epithelial cells; binding site; trans-activators; dna microarray; gene induction; wnt proteins; beta catenin; wnt protein; anchorage independent growth; apc protein; fibroblast growth factor; fibroblast growth factor 20; fibroblast growth factors; t cell factor protein; normal human; cytoskeletal proteins; xenopus laevis; wnt signaling; β-catenin; intestinal mucosa; xenopus proteins; promoter regions (genetics); dkk1; fgf-20; lymphoid enhancer factor; dkk1 gene; fgf20 gene |
| Journal Title: | EMBO Journal |
| Volume: | 24 |
| Issue: | 1 |
| ISSN: | 0261-4189 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2005-01-01 |
| Start Page: | 73 |
| End Page: | 84 |
| Language: | English |
| DOI: | 10.1038/sj.emboj.7600460 |
| PUBMED: | 15592430 |
| PROVIDER: | scopus |
| PMCID: | PMC544900 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 134" - "Export Date: 24 October 2012" - "CODEN: EMJOD" - "Source: Scopus" |
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