FOXP3 Is an X-Linked Breast Cancer Suppressor Gene and an Important Repressor of the HER-2/ErbB2 Oncogene
نویسندگان
چکیده
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 (Foxp3(sf/+)) 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.
منابع مشابه
FOXP3 is a novel transcriptional repressor for the breast cancer oncogene SKP2.
S-phase kinase-associated protein 2 (SKP2) is a component of the E3 ubiquitin ligase SKP1-Cul1-Fbox complex. Overexpression of SKP2 results in cell cycle dysregulation and carcinogenesis; however, the genetic lesions that cause this upregulation are poorly understood. We recently demonstrated that forkhead box P3 (FOXP3) is an X-linked breast cancer suppressor and an important repressor of the ...
متن کاملThe X Factor: Skewing X Inactivation towards Cancer
Increased expression of the epidermal growth factor receptor HER-2/ErbB2 is frequently observed in breast cancer and is targeted by the anticancer drug Herceptin. Now, Zuo et al. (2007) reveal that an X-linked gene encoding the transcription factor FOXP3 is a breast cancer tumor suppressor that represses expression of HER2/ErbB2.
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FOXP3 is an X-linked tumor suppressor gene and amaster regulator in T regulatory cell function. This gene has been found to be mutated frequently in breast and prostate cancers and to inhibit tumor cell growth, but its functional significance in DNA repair has not been studied. We found that FOXP3 silencing stimulates homologous recombination-mediated DNA repair and also repair of g-irradiation...
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ورودعنوان ژورنال:
- Cell
دوره 129 شماره
صفحات -
تاریخ انتشار 2007