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, Scopus)

  • 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: BRI3, HCC, HSF2, Wnt/TCF4/β-catenin targets, Xenograft
  • Boğaziçi Üniversitesi Adresli: Evet

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. 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. © 2010 Elsevier Inc.