FOXP3 is an X-linked breast cancer suppressor gene and an important repressor of the HER-2/ErbB2 oncogene

被引：362

作者：

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 ^{[1
]}

Liu, Yang

机构：

[1] Univ Michigan, Ctr Comprehens Canc, Dept Surg, Sect Gen Surg,Div Immunotherapy, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Program Mol Mech Dis, Ann Arbor, MI 48109 USA

[3] Ohio State Univ, Med Ctr, Dept Virol Immunol & Med Genet, Program Mol Cellular & Dev Biol, Columbus, OH 43210 USA

[4] Ohio State Univ, Med Ctr, Dept Pathol, Columbus, OH 43210 USA

[5] Ohio State Univ, Med Ctr, Dept Internal Med, Columbus, OH 43210 USA

[6] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA

[7] Univ N Carolina, Dept Pathol, Chapel Hill, NC 27599 USA

[8] Univ Michigan, Dept Biol & Mat Sci, Lab Mol Signaling & Apoptosis, Sch Dent, Ann Arbor, MI 48109 USA

来源：

CELL | 2007年 / 129卷 / 07期

关键词：

D O I：

10.1016/j.cell.2007.04.034

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1275 / 1286

页数：12

共 35 条

[1] The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3 [J].