1. Analysis of the Wnt/B-catenin/TCF4 pathway using SAGE, genome-wide microarray and promoter analysis: Identification of BRI3 and HSF2 as novel targets
- Author
-
Kavak, Ersen, Najafov, Ayaz, Ozturk, Nuri, Seker, Tuncay, Cavusoglu, Kader, Aslan, Tolga, Duru, Adil Doganay, Saygili, Tahsin, Hoxhaj, Gerta, Hiz, Mahmut Can, Unal, Durisehvar Ozer, Birgül-İyison, Necla, Ozturk, Mehmet, and Koman, Ahmet
- Subjects
- *
CELLULAR signal transduction , *WNT proteins , *XENOGRAFTS , *EMBRYOLOGY , *PROMOTERS (Genetics) , *GENE expression , *DNA microarrays , *GENOMES - Abstract
Abstract: The Wnt signaling pathway is involved in many differentiation events during embryonic development and can lead to tumor formation after aberrant activation of its components. β-catenin, a cytoplasmic component, plays a major role in the transduction of canonical Wnt signaling. The aim of this study was to identify novel genes that are regulated by active β-catenin/TCF signaling in hepatocellular carcinoma-derived Huh7 cells with high (transfected) and low β-catenin/TCF activities. High TCF activity Huh7 cells led to earlier and larger tumor formation when xenografted into nude mice. SAGE (Serial Analysis of Gene Expression), genome-wide microarray and in silico promoter analysis were performed in parallel, to compare gene expression between low and high β-catenin/TCF activity clones, and also those that had been rescued from the xenograft tumors. SAGE and genome-wide microarray data were compared and contrasted. BRI3 and HSF2 were identified as novel targets of Wnt/β-catenin signaling after combined analysis and confirming experiments including qRT-PCR, ChIP, luciferase assay and lithium treatment. [Copyright &y& Elsevier]
- Published
- 2010
- Full Text
- View/download PDF