Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2000-4-26
pubmed:abstractText
The adenomatous polyposis coli (APC) gene, a member of the Wingless/Wnt signal transduction pathway, has been implicated in the development of medulloblastomas in Turcot's syndrome. beta-catenin also functions in this highly conserved signaling pathway and is instrumental in growth and development. Mutations in either APC or beta-catenin can stabilize beta-catenin protein. Stabilized beta-catenin complexes with Tcf/Lef transcription factors and moves from the cytoplasm into the nucleus where it regulates the transcription of c-Myc and other genes. Nuclear localization of beta-catenin therefore implies activation of the signaling pathway. We have analyzed the subcellular localization of beta-catenin in 51 sporadic medulloblastomas and in 1 medulloblastoma arising in a patient with Turcot's syndrome. Nuclear beta-catenin staining was present in 9 of the sporadic tumors (18%) and in the 1 medulloblastoma from a Turcot's patient. The remaining 41 cases did not show nuclear staining. This confirms earlier observations that Wingless/Wnt signaling is involved in a subset of sporadic medulloblastomas. We also examined 48 glial and meningeal CNS tumors, all of which were negative for nuclear beta-catenin. Exon 3 of beta-catenin was sequenced in 6 of the 9 sporadic medulloblastomas with nuclear beta-catenin staining. Five of the 6 tumors sequenced had mutations affecting highly conserved beta-catenin phosphorylation sites involved in protein stability. These data suggest a simple immunohistochemical method to screen for beta-catenin mutations in medulloblastomas.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-3069
pubmed:author
pubmed:issnType
Print
pubmed:volume
59
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
333-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10759189-Aged, pubmed-meshheading:10759189-Binding Sites, pubmed-meshheading:10759189-Cell Nucleus, pubmed-meshheading:10759189-Central Nervous System Neoplasms, pubmed-meshheading:10759189-Cytoplasm, pubmed-meshheading:10759189-Cytoskeletal Proteins, pubmed-meshheading:10759189-DNA Mutational Analysis, pubmed-meshheading:10759189-Exons, pubmed-meshheading:10759189-Fetal Diseases, pubmed-meshheading:10759189-Humans, pubmed-meshheading:10759189-Immunohistochemistry, pubmed-meshheading:10759189-Medulloblastoma, pubmed-meshheading:10759189-Middle Aged, pubmed-meshheading:10759189-Mutation, pubmed-meshheading:10759189-Phosphorylation, pubmed-meshheading:10759189-Polymerase Chain Reaction, pubmed-meshheading:10759189-Proto-Oncogene Proteins, pubmed-meshheading:10759189-Signal Transduction, pubmed-meshheading:10759189-Survival Rate, pubmed-meshheading:10759189-Trans-Activators, pubmed-meshheading:10759189-Wnt Proteins, pubmed-meshheading:10759189-Zebrafish Proteins, pubmed-meshheading:10759189-beta Catenin
pubmed:year
2000
pubmed:articleTitle
Nuclear localization and mutation of beta-catenin in medulloblastomas.
pubmed:affiliation
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't