FOXP3 Is an X-Linked Breast Cancer Suppressor Gene and an Important Repressor of the HER-2/ErbB2 Oncogene
FOXP3 Is an X-Linked Breast Cancer Suppressor Gene and an Important Repressor of the HER-2/ErbB2 Oncogene
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DOI：
10.1016/j.cell.2008.07.036
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发表时间：
2008-08
期刊：
影响因子：
64.5
通讯作者：
T. Zuo;Lizhong Wang;C. Morrison;Xing Chang;Huiming Zhang;Yan Liu;Yin Wang;Xingluo Liu;M. Ch
中科院分区：
文献类型：
--
作者：
T. Zuo;Lizhong Wang;C. Morrison;Xing Chang;Huiming Zhang;Yan Liu;Yin Wang;Xingluo Liu;M. Ch
X-linkedFoxp 3是叉头/翼状螺旋转录因子家族的成员。生殖系突变导致男性致命的自身免疫性疾病。偶然地，我们观察到Foxp 3基因的“scurfin”突变（Foxp 3sf/+）杂合子的雌性小鼠以高比率发展癌症。大多数乳腺癌中野生型Foxp 3等位基因失活，HER-2/ErbB 2过表达。Foxp 3结合并抑制HER-2/ErbB 2启动子。FOXP 3基因的缺失、功能显著的体细胞突变和下调在人类乳腺癌样本中普遍存在，并且与HER-2/ErbB 2过表达显著相关，无论HER-2扩增的状态如何。我们的数据表明FOXP 3是一个X连锁的乳腺癌抑制基因，是HER-2/ErbB 2癌基因的重要调节因子。
The X-linkedFoxp3is 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 theFoxp3gene (Foxp3sf/+) developed cancer at a high rate. The majority of the cancers were mammary carcinomas in which the wild-typeFoxp3allele was inactivated andHER-2/ErbB2was overexpressed. Foxp3 bound and repressed theHER-2/ErbB2promoter. Deletion, functionally significant somatic mutations, and downregulation of theFOXP3gene were commonly found in human breast cancer samples and correlated significantly with HER-2/ErbB2 overexpression, regardless of the status ofHER-2amplification. Our data demonstrate thatFOXP3is an X-linked breast cancer suppressor gene and an important regulator of theHER-2/ErbB2oncogene.