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Nat Med. 2006 Apr;12(4):395-7. Epub 2006 Mar 26.

Human sebaceous tumors harbor inactivating mutations in LEF1.

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1
Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.

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.

PMID:
16565724
DOI:
10.1038/nm1386
[Indexed for MEDLINE]
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