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PMID: 16565724 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Human sebaceous tumors harbor inactivating mutations in LEF1.

Nature medicine ·Vol. 12 ·No. 4 ·2006-04-00 ·Pages 395-7

Takeda H, Lyle S, Lazar AJ, Zouboulis CC, Smyth I, Watt FM

Abstract

We found that one-third of human sebaceous tumors examined had double-nucleotide substitutions in the same LEF1 allele, irrespective of DNA mismatch repair status. The mutations impaired both LEF1 binding to beta-catenin and transcriptional activation, and are the first tumor-associated mutations that inactivate Wnt signaling. Mutant LEF1 not only inhibited expression of beta-catenin target genes but also stimulated expression of sebocyte markers, suggesting that it may determine the differentiated characteristics of sebaceous tumors.

MeSH Terms
Adenoma/pathology Alleles Amino Acid Sequence Amino Acid Substitution Base Sequence Cell Line Conserved Sequence DNA/analysis,genetics Gene Expression Regulation, Neoplastic Genes, Reporter Genetic Markers Humans Luciferases/analysis,metabolism Lymphoid Enhancer-Binding Factor 1/analysis,genetics,metabolism Molecular Sequence Data Sebaceous Gland Neoplasms/genetics,metabolism,pathology Sequence Analysis, DNA Sequence Homology, Amino Acid Signal Transduction Transcription, Genetic Transcriptional Activation Wnt Proteins/metabolism beta Catenin/analysis,genetics,metabolism
Chemicals
Genetic Markers Lymphoid Enhancer-Binding Factor 1 Wnt Proteins beta Catenin DNA Luciferases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Takeda Hikaru
Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Lyle Stephen
Lazar Alexander J F
Zouboulis Christos C
Smyth Ian
Watt Fiona M
Article Info
Journal
Nature medicine
Abbr.
Nat Med
ISSN
1078-8956
DOI
10.1038/nm1386
Published
2006-04-00
Epub
2006-00-26
Pages
395-7
Language
English
Region
United States
NLM ID
9502015
Subset
IM
Grants
NIAMS NIH HHS · AR02179 · United States
NIAMS NIH HHS · P30AR042689 · United States
External Links
PubMed source DOI: 10.1038/nm1386 View journal details
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