Analysis of the Wnt/B-catenin/TCF4 pathway using SAGE, genome-wide microarray and promoter analysis: Identification of BRI3 and HSF2 as novel targets

作者：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; Birgul Iyison Necla; Ozturk Mehmet; Koman Ahmet

来源：Cellular Signalling, 2010, 22(10): 1523-1535.

DOI：10.1016/j.cellsig.2010.05.021

• Wnt/TCF4/beta-catenin targets
• HCC
• BRI3
• HSF2
• Xenograft

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. beta-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 beta-catenin/TCF signaling in hepatocellular carcinoma-derived Huh7 cells with high (transfected) and low beta-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 beta-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/beta-catenin signaling after combined analysis and confirming experiments including qRT-PCR, ChIP, luciferase assay and lithium treatment.

• 出版日期2010-10