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

Kavak E., Najafov A., Ozturk N., Seker T., Cavusoglu K., Aslan T., ...Daha Fazla

CELLULAR SIGNALLING, cilt.22, sa.10, ss.1523-1535, 2010 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 22 Sayı: 10
  • Basım Tarihi: 2010
  • Doi Numarası: 10.1016/j.cellsig.2010.05.021
  • Dergi Adı: CELLULAR SIGNALLING
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1523-1535
  • Anahtar Kelimeler: Wnt/TCF4/beta-catenin targets, HCC, BRI3, HSF2, Xenograft, HEPATOCELLULAR-CARCINOMA CELLS, WNT/BETA-CATENIN PATHWAY, GENE-EXPRESSION, BETA-CATENIN, TRANSCRIPTION FACTORS, COLORECTAL-CANCER, SIGNALING PATHWAY, SIDE POPULATION, WNT, LIVER
  • İstanbul Üniversitesi Adresli: Hayır

Özet

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. (C) 2010 Elsevier Inc. All rights reserved.