Human sebaceous tumors harbor inactivating mutations in LEF1.
basic_science · Level V
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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.
Medical subject headings
- Amino Acid Substitution
- Lymphoid Enhancer-Binding Factor 1
- Sebaceous Gland Neoplasms
- Transcriptional Activation
- beta Catenin