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 (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.
authors.affiliation: 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.
authors.forename: Tao
authors.initials: T
authors.lastname: Zuo
authors.forename: Lizhong
authors.initials: L
authors.lastname: Wang
authors.forename: Carl
authors.initials: C
authors.lastname: Morrison
authors.forename: Xing
authors.initials: X
authors.lastname: Chang
authors.forename: Huiming
authors.initials: H
authors.lastname: Zhang
authors.forename: Weiquan
authors.initials: W
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.forename: Xingluo
authors.initials: X
authors.lastname: Liu
authors.forename: Michael W Y
authors.initials: MW
authors.lastname: Chan
authors.forename: Jin-Qing
authors.initials: JQ
authors.lastname: Liu
authors.forename: Richard
authors.initials: R
authors.lastname: Love
authors.forename: Chang-Gong
authors.initials: CG
authors.lastname: Liu
authors.forename: Virginia
authors.initials: V
authors.lastname: Godfrey
authors.forename: Rulong
authors.initials: R
authors.lastname: Shen
authors.forename: Tim H-M
authors.initials: TH
authors.lastname: Huang
authors.forename: Tianyu
authors.initials: T
authors.lastname: Yang
authors.forename: Bae Keun
authors.initials: BK
authors.lastname: Park
authors.forename: Cun-Yu
authors.initials: CY
authors.lastname: Wang
authors.forename: Pan
authors.initials: P
authors.lastname: Zheng
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D041321:Chromosomes, Human, X / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D050172:Genes, X-Linked / Q000235:genetics*; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics; D049951:X Chromosome Inactivation / Q000235:genetics
chemical_list: D051858:Forkhead Transcription Factors; D018719:Erb-b2 Receptor Tyrosine Kinases; D025521:Tumor Suppressor Proteins; C418974:FOXP3 protein, human; C508053:ERBB2 protein, human