Abstract
The X-linked Foxp3 is a member of the forkhead/winged helix transcription factor family. Germline mutations cause lethal autoimmune diseases in males. Serendipitously, we observed that female mice heterozygous for the "scurfin" mutation of the Foxp3 gene (Foxp3sf/+) developed cancer at a high rate. The majority of the cancers were mammary carcinomas in which the wild-type Foxp3 allele was inactivated and HER-2/ErbB2 was overexpressed. Foxp3 bound and repressed the HER-2/ErbB2 promoter. Deletion, functionally significant somatic mutations, and downregulation of the FOXP3 gene were commonly found in human breast cancer samples and correlated significantly with HER-2/ErbB2 overexpression, regardless of the status of HER-2 amplification. Our data demonstrate that FOXP3 is an X-linked breast cancer suppressor gene and an important regulator of the HER-2/ErbB2 oncogene.
Original language | English (US) |
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Pages (from-to) | 1275-1286 |
Number of pages | 12 |
Journal | Cell |
Volume | 129 |
Issue number | 7 |
DOIs | |
State | Published - Jun 29 2007 |
Externally published | Yes |
Keywords
- HUMDISEASE
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)