title: AXIN1 Expression and Localization in Meningiomas and Association to Changes of APC and E-cadherin.
abstract: Tumor suppressor gene AXIN1 is an inhibitor of Wnt signaling pathway. It down-regulates the pathway's main signaling effector molecule, beta-catenin, in an AXIN-based destruction complex. In the present study we investigated the involvement of AXIN1 in intracranial meningioma.
  
  
  
  Loss of heterozygosity and microsatellite instability analyses were performed. The consequences of genetic changes on protein expression levels were studied in the same patients by immunohistochemistry.
  
  
  
  Allelic deletions of AXIN1 gene were found in 21.1% of meningiomas. Microsatellite instability was also observed in 5.3% of cases. Weak or lack of AXIN1 expression was found in 21.9% of meningiomas. We found strong statistical correlations between cytoplasmic localization of AXIN1 and its weak expression and also between the simultaneous cytoplasmic and nuclear localizations and moderate and strong expression levels (p<0.000). The findings on AXIN1 were compared to concomitant expression of APC, beta-catenin and E-cadherin in the same patients by Chi-Square tests and Pearson's correlations. Analysis revealed that AXIN1 genetic changes were significantly associated to lack of the expression of APC and presence of mutant APC proteins (p<0.018). Moderate and strong cytoplasmic and nuclear AXIN1 expressions were positively correlated to strong expression of E-cadherin (p<0.05).
  
  
  
  Our findings on genetic changes and expression levels of AXIN1 bring novel data on its involvement in meningeal brain tumors and reveal AXIN1's relation to specific Wnt molecules.
authors.affiliation: Laboratory of Neurooncology, Croatian Institute for Brain Research, School of Medicine University of Zagreb, Zagreb, Croatia Department of Biology, School of Medicine, University of Zagreb, Zagreb, Croatia nina@mef.hr.
authors.forename: Nives
authors.initials: N
authors.lastname: Pećina-Šlaus
authors.affiliation: Laboratory of Neurooncology, Croatian Institute for Brain Research, School of Medicine University of Zagreb, Zagreb, Croatia Department of Biology, School of Medicine, University of Zagreb, Zagreb, Croatia.
authors.forename: Anja
authors.initials: A
authors.lastname: Kafka
authors.affiliation: Department of Biochemical Engineering, Faculty of Food Technology and Biotechnology, University of Zagreb, Zagreb, Croatia.
authors.forename: Tomislav
authors.initials: T
authors.lastname: Vladušić
authors.affiliation: Department of Radiology, Hospital Center "Sisters of Mercy", Zagreb, Croatia.
authors.forename: Hrvoje Ivan
authors.initials: HI
authors.lastname: Pećina
authors.affiliation: Department of Biochemical Engineering, Faculty of Food Technology and Biotechnology, University of Zagreb, Zagreb, Croatia.
authors.forename: Reno
authors.initials: R
authors.lastname: Hrašćan
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000483:Alleles; D015703:Antigens, CD; D060466:Axin Protein / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D008579:Meningioma / Q000378:metabolism*; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D015398:Signal Transduction; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: C555337:APC protein, human; C555451:AXIN1 protein, human; D025601:Adenomatous Polyposis Coli Protein; D015703:Antigens, CD; D060466:Axin Protein; C513384:CDH1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D051176:beta Catenin
keywords: AXIN1; Wnt signaling; immunohistochemistry; loss of heterozygosity; meningiomas