Author/Authors :
Tao Zuo، نويسنده , , Lizhong Wang، نويسنده , , Carl Morrison، نويسنده , , Xing Chang، نويسنده , , Huiming Zhang، نويسنده , , Weiquan Li، نويسنده , , Yan Liu، نويسنده , , Yin Wang، نويسنده , , Xingluo Liu، نويسنده , , Michael W.Y. Chan، نويسنده , , Jin-Qing Liu، نويسنده , , Richard Love، نويسنده , , Chang-gong Liu، نويسنده , , Virginia Godfrey، نويسنده , , Rulong Shen، نويسنده , , Tim H.-M. Huang، نويسنده , , Tianyu Yang and Wasfy B. Mikhael، نويسنده , , Bae Keun Park، نويسنده , , Cun-Yu Wang، نويسنده , , Pan Zheng، نويسنده , , et al.، نويسنده ,
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.
