Zuo Tao, Wang Lizhong, Morrison Carl, Chang Xing, Zhang Huiming, Li Weiquan, Liu Yan, Wang Yin, Liu Xingluo, Chan Michael W Y, Liu Jin-Qing, Love Richard, Liu Chang-Gong, Godfrey Virginia, Shen Rulong, Huang Tim H-M, Yang Tianyu, Park Bae Keun, Wang Cun-Yu, Zheng Pan, Liu Yang
Program in Molecular, Cellular, and Developmental Biology and Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University Medical Center and Comprehensive Cancer Center, Columbus, OH 43210, USA.
Cell. 2007 Jun 29;129(7):1275-86. doi: 10.1016/j.cell.2007.04.034. Epub 2007 Jun 14.
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.
X连锁的Foxp3是叉头/翼状螺旋转录因子家族的成员。种系突变会导致男性患致命的自身免疫性疾病。偶然地，我们观察到Foxp3基因“scurfin”突变的杂合雌性小鼠（Foxp3(sf/+)）患癌率很高。大多数癌症是乳腺癌，其中野生型Foxp3等位基因失活，HER-2/ErbB2过表达。Foxp3结合并抑制HER-2/ErbB2启动子。在人类乳腺癌样本中常见FOXP3基因的缺失、具有功能意义的体细胞突变和下调，并且与HER-2/ErbB2过表达显著相关，而与HER-2扩增状态无关。我们的数据表明FOXP3是一个X连锁的乳腺癌抑制基因，也是HER-2/ErbB2癌基因的重要调节因子。
