Role of Wnt pathway in medulloblastoma oncogenesis.
To clarify the roles of Wnt pathway in medulloblastoma oncogenesis, immunohistochemical staining of beta-catenin and Wnt-1 and genomic analyses of CTNNB1 (beta-catenin) and AXIN1 (axin 1) were examined in 23 sporadic cases. Accumulation of beta-catenin in tumor cells was immunohistochemically proven in 5 cases; 2 cases showed positive immunoreactivity for Wnt-1 and another 2 showed mutation of either CTNNB1 or AXIN1. AXIN1 mutation was in exon 3, corresponding to GSK-3beta binding site and CTNNB1 mutation was in exon 3, corresponding to its phosphorylation site. Disruption of these proteins could result in upregulation of the Wnt signaling and accumulation of beta-catenin, followed by cell proliferation and medulloblastoma oncogenesis.
Yokota
Naoki
N
Department of Neurosurgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
Nishizawa
Shigeru
S
Ohta
Seiji
S
Date
Hiroaki
H
Sugimura
Haruhiko
H
Namba
Hiroki
H
Maekawa
Masato
M
D060466:Axin Protein; D001483:Base Sequence; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008527:Medulloblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics*; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin
C555451:AXIN1 protein, human; D060466:Axin Protein; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; C495247:WNT1 protein, human; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin