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

Tao Zuo; Lizhong Wang; Carl Morrison; Xing Chang; Huiming Zhang; Weiquan Li; Yan Liu; Yin Wang; Xingluo Liu; Michael W.Y. Chan; Jin Qing Liu; Richard Love; Chang gong Liu; Virginia Godfrey; Rulong Shen; Tim H.M. Huang; Tianyu Yang; Bae Keun Park; Cun Yu Wang; Pan Zheng; Yang Liu

doi:10.1016/j.cell.2007.04.034

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

Tao Zuo, Lizhong Wang, Carl Morrison, Xing Chang, Huiming Zhang, Weiquan Li, Yan Liu, Yin Wang, Xingluo Liu, Michael W.Y. Chan, Jin Qing Liu, Richard Love, Chang gong Liu, Virginia Godfrey, Rulong Shen, Tim H.M. Huang, Tianyu Yang, Bae Keun Park, Cun Yu Wang, Pan ZhengYang Liu

Molecular Medicine

Research output: Contribution to journal › Article › peer-review

296 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1275-1286
Number of pages	12
Journal	Cell
Volume	129
Issue number	7
DOIs	https://doi.org/10.1016/j.cell.2007.04.034
State	Published - Jun 29 2007

Keywords

HUMDISEASE

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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Zuo, T., Wang, L., Morrison, C., Chang, X., Zhang, H., Li, W., Liu, Y., Wang, Y., Liu, X., Chan, M. W. Y., Liu, J. Q., Love, R., Liu, C. G., Godfrey, V., Shen, R., Huang, T. H. M., Yang, T., Park, B. K., Wang, C. Y., ... Liu, Y. (2007). FOXP3 Is an X-Linked Breast Cancer Suppressor Gene and an Important Repressor of the HER-2/ErbB2 Oncogene. Cell, 129(7), 1275-1286. https://doi.org/10.1016/j.cell.2007.04.034

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

In: Cell, Vol. 129, No. 7, 29.06.2007, p. 1275-1286.

Research output: Contribution to journal › Article › peer-review

Zuo, T, Wang, L, Morrison, C, Chang, X, Zhang, H, Li, W, Liu, Y, Wang, Y, Liu, X, Chan, MWY, Liu, JQ, Love, R, Liu, CG, Godfrey, V, Shen, R, Huang, THM, Yang, T, Park, BK, Wang, CY, Zheng, P & Liu, Y 2007, 'FOXP3 Is an X-Linked Breast Cancer Suppressor Gene and an Important Repressor of the HER-2/ErbB2 Oncogene', Cell, vol. 129, no. 7, pp. 1275-1286. https://doi.org/10.1016/j.cell.2007.04.034

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. / FOXP3 Is an X-Linked Breast Cancer Suppressor Gene and an Important Repressor of the HER-2/ErbB2 Oncogene. In: Cell. 2007 ; Vol. 129, No. 7. pp. 1275-1286.

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title = "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 (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.",

keywords = "HUMDISEASE",

author = "Tao Zuo and Lizhong Wang and Carl Morrison and Xing Chang and Huiming Zhang and Weiquan Li and Yan Liu and Yin Wang and Xingluo Liu and Chan, {Michael W.Y.} and Liu, {Jin Qing} and Richard Love and Liu, {Chang gong} and Virginia Godfrey and Rulong Shen and Huang, {Tim H.M.} and Tianyu Yang and Park, {Bae Keun} and Wang, {Cun Yu} and Pan Zheng and Yang Liu",

note = "Funding Information: We thank Dr. Fan Meng for assistance in bioinformatics, Drs. Eric Fearon, Albert de la Chapelle, Zhaohui Qin, Michael Caligiuri, and Charis Eng for their valuable discussions and/or critical reading of the manuscript, and Lynde Shaw for secretarial assistance. This study is supported by grants from the National Institutes of Health and the Department of Defense. ",

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AU - Zuo, Tao

AU - Wang, Lizhong

AU - Morrison, Carl

AU - Chang, Xing

AU - Zhang, Huiming

AU - Li, Weiquan

AU - Liu, Yan

AU - Wang, Yin

AU - Liu, Xingluo

AU - Chan, Michael W.Y.

AU - Liu, Jin Qing

AU - Love, Richard

AU - Liu, Chang gong

AU - Godfrey, Virginia

AU - Shen, Rulong

AU - Huang, Tim H.M.

AU - Yang, Tianyu

AU - Park, Bae Keun

AU - Wang, Cun Yu

AU - Zheng, Pan

AU - Liu, Yang

N1 - Funding Information: We thank Dr. Fan Meng for assistance in bioinformatics, Drs. Eric Fearon, Albert de la Chapelle, Zhaohui Qin, Michael Caligiuri, and Charis Eng for their valuable discussions and/or critical reading of the manuscript, and Lynde Shaw for secretarial assistance. This study is supported by grants from the National Institutes of Health and the Department of Defense.

PY - 2007/6/29

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N2 - 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.

AB - 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.

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