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

Academic Article

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.
  • Published In

  • Cell  Journal
  • Keywords

  • Animals, Breast Neoplasms, Carcinoma, Cell Line, Tumor, Chromosomes, Human, X, Down-Regulation, Female, Forkhead Transcription Factors, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, Genes, X-Linked, Genes, erbB-2, Humans, Mammary Neoplasms, Experimental, Mice, Mice, Inbred BALB C, Mice, Mutant Strains, Mutation, Promoter Regions, Genetic, Receptor, ErbB-2, Tumor Suppressor Proteins, X Chromosome Inactivation
  • Digital Object Identifier (doi)

    Author List

  • Zuo T; Wang L; Morrison C; Chang X; Zhang H; Li W; Liu Y; Wang Y; Liu X; Chan MWY
  • Start Page

  • 1275
  • End Page

  • 1286
  • Volume

  • 129
  • Issue

  • 7