FOXP3 Is an X-Linked Breast Cancer Suppressor Gene and an Important Repressor of the HER-2/ErbB2 Oncogene

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 (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.

DOI: 10.1016/j.cell.2008.07.036

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@article{Zuo2007FOXP3IA, title={FOXP3 Is an X-Linked Breast Cancer Suppressor Gene and an Important Repressor of the HER-2/ErbB2 Oncogene}, author={Tao Zuo and Lizhong Wang and Carl D. Morrison and Xing Chang and Huiming Zhang and Yan Liu and Yin Wang and Xingluo Liu and Michael W.Y. Chan and Jin-qing Liu and Richard J . Love and Virginia L. Godfrey and Rulong Z. Shen and Tim H. M. Huang and Tianyu Yang and Pan Zheng and Yang Liu}, journal={Cell}, year={2007}, volume={129}, pages={1275-1286} }