Linked Life Data

10192393

Source:http://linkedlifedata.com/resource/pubmed/id/10192393

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1999-4-26
pubmed:abstractText
WNT signalling orchestrates a number of developmental programs. In response to this stimulus, cytoplasmic beta-catenin (encoded by CTNNB1) is stabilized, enabling downstream transcriptional activation by members of the LEF/TCF family. One of the target genes for beta-catenin/TCF encodes c-MYC, explaining why constitutive activation of the WNT pathway can lead to cancer, particularly in the colon. Most colon cancers arise from mutations in the gene encoding adenomatous polyposis coli (APC), a protein required for ubiquitin-mediated degradation of beta-catenin, but a small percentage of colon and some other cancers harbour beta-catenin-stabilizing mutations. Recently, we discovered that transgenic mice expressing an activated beta-catenin are predisposed to developing skin tumours resembling pilomatricomas. Given that the skin of these adult mice also exhibits signs of de novo hair-follicle morphogenesis, we wondered whether human pilomatricomas might originate from hair matrix cells and whether they might possess beta-catenin-stabilizing mutations. Here, we explore the cell origin and aetiology of this common human skin tumour. We found nuclear LEF-1 in the dividing tumour cells, providing biochemical evidence that pilomatricomas are derived from hair matrix cells. At least 75% of these tumours possess mutations affecting the amino-terminal segment, normally involved in phosphorylation-dependent, ubiquitin-mediated degradation of the protein. This percentage of CTNNB1 mutations is greater than in all other human tumours examined thus far, and directly implicates beta-catenin/LEF misregulation as the major cause of hair matrix cell tumorigenesis in humans.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1061-4036
pubmed:author
pubmed:issnType
Print
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
410-3
pubmed:dateRevised
2008-8-29
pubmed:meshHeading
pubmed-meshheading:10192393-Amino Acid Sequence, pubmed-meshheading:10192393-Cytoskeletal Proteins, pubmed-meshheading:10192393-DNA-Binding Proteins, pubmed-meshheading:10192393-Deoxyribonucleases, Type II Site-Specific, pubmed-meshheading:10192393-Gene Frequency, pubmed-meshheading:10192393-Hair Diseases, pubmed-meshheading:10192393-Humans, pubmed-meshheading:10192393-Lymphoid Enhancer-Binding Factor 1, pubmed-meshheading:10192393-Molecular Sequence Data, pubmed-meshheading:10192393-Mutation, pubmed-meshheading:10192393-Pilomatrixoma, pubmed-meshheading:10192393-Polymerase Chain Reaction, pubmed-meshheading:10192393-Sequence Analysis, DNA, pubmed-meshheading:10192393-Skin Neoplasms, pubmed-meshheading:10192393-Trans-Activators, pubmed-meshheading:10192393-Transcription Factors, pubmed-meshheading:10192393-beta Catenin
pubmed:year
1999
pubmed:articleTitle
A common human skin tumour is caused by activating mutations in beta-catenin.
pubmed:affiliation
Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, The University of Chicago, Illinois 60637, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't