FOXP3 is an X-linked breast cancer suppressor gene and an important repressor of the HER-2/ErbB2 oncogene.
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.
Zuo
Tao
T
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.
Wang
Lizhong
L
Morrison
Carl
C
Chang
Xing
X
Zhang
Huiming
H
Li
Weiquan
W
Liu
Yan
Y
Wang
Yin
Y
Liu
Xingluo
X
Chan
Michael W Y
MW
Liu
Jin-Qing
JQ
Love
Richard
R
Liu
Chang-Gong
CG
Godfrey
Virginia
V
Shen
Rulong
R
Huang
Tim H-M
TH
Yang
Tianyu
T
Park
Bae Keun
BK
Wang
Cun-Yu
CY
Zheng
Pan
P
Liu
Yang
Y
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
D051858:Forkhead Transcription Factors; D018719:Erb-b2 Receptor Tyrosine Kinases; D025521:Tumor Suppressor Proteins; C418974:FOXP3 protein, human; C508053:ERBB2 protein, human