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

Autor: Kavak E; Department of Molecular Biology and Genetics, Bogazici University, Istanbul, Turkey. ersen.kavak@ki.se, Najafov A, Ozturk N, Seker T, Cavusoglu K, Aslan T, Duru AD, Saygili T, Hoxhaj G, Hiz MC, Unal DO, Birgül-Iyison N, Ozturk M, Koman A
Jazyk: angličtina
Zdroj: Cellular signalling [Cell Signal] 2010 Oct; Vol. 22 (10), pp. 1523-35. Date of Electronic Publication: 2010 Jun 09.
DOI: 10.1016/j.cellsig.2010.05.021
Abstrakt: 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.
(Copyright 2010 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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