title: WNT/β-catenin Signaling Pathway and Downstream Modulators in Low- and High-grade Glioma.
abstract: BACKGROUND
  Aberrant activation of the canonical Wingless-type MMTV integration site family (WNT)/β-catenin signaling pathway is critical for gliomas.
  
  
  METHODS
  In 74 gliomas of different histological grade and in 24 glioblastoma cell lines, protein expression of WNT member 3a (WNT3a), β-catenin and transcription factor 4 (TCF4) was investigated by immunohistochemistry, western blotting, immunofluorescence and immunocytochemistry. In tumors and cell lines, WNT3A expression was assessed at the mRNA level by quantitative real-time polymerase chain reaction.
  
  
  RESULTS
  WNT3a was overexpressed at the protein and mRNA levels in malignant astrocytic tumors and cell lines. Cytoplasmic expression of β-catenin was detected in high-grade gliomas and cell lines, with evidence of nuclear translocation on fractionated protein extracts. Activating mutations in the β-catenin encoding gene (CTNNB1) were excluded by direct sequencing. TCF4 was statistically correlated with Ki-67/MIB-1 and cyclin D1 labeling indices.
  
  
  CONCLUSIONS
  Expression of WNT3a, cytoplasmic β-catenin and TCF4 was significantly associated with the histological malignancy grade and with a worse prognosis for patients with glioma.
authors.affiliation: Research Center, Polyclinic of Monza Foundation, Vercelli, Italy Department of Neurosurgery, CTO Hospital/Health and Science City, Turin, Italy.
authors.forename: Tetyana
authors.initials: T
authors.lastname: Denysenko
authors.affiliation: Research Center, Polyclinic of Monza Foundation, Vercelli, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Annovazzi
authors.affiliation: Department of Medical Sciences, University of Turin/Health and Science City, Turin, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Cassoni
authors.affiliation: Department of Neurosurgery, CTO Hospital/Health and Science City, Turin, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Melcarne
authors.affiliation: Research Center, Polyclinic of Monza Foundation, Vercelli, Italy marta.mellai@cnbo.it.
authors.forename: Marta
authors.initials: M
authors.lastname: Mellai
authors.affiliation: Research Center, Polyclinic of Monza Foundation, Vercelli, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Schiffer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway; D060509:Wnt3A Protein / Q000235:genetics / Q000378:metabolism; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D012333:RNA, Messenger; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; C555510:WNT3A protein, human; D060509:Wnt3A Protein; D051176:beta Catenin
keywords: Gliomas; TCF4; WNT3a; glioblastoma multiforme; prognosis; β-catenin