INTRODUCTION: The chromodomain helicase DNA binding protein 5 (CHD5) has 
recently been identified as a tumor suppressor in a mouse model. The CHD5 locus 
at 1p36 is deleted, and its mutation has been detected in breast cancer. We, 
therefore, evaluated whether CHD5 plays a role in human breast cancer.
METHODS: We screened mutations in 55 tumors, determined promoter methylation in 
39 tumors, measured RNA expression in 90 tumors, analyzed protein expression in 
289 tumors, and correlated expression changes with clinicopathological 
characteristics of breast cancer. Functional effects of CHD5 on cell 
proliferation, invasion and tumorigenesis were also tested.
RESULTS: Although only one mutation was detected, CHD5 mRNA expression was 
significantly reduced, accompanied by frequent genomic deletion and promoter 
methylation, in breast cancer. The extent of methylation was significantly 
associated with reduced mRNA expression, and demethylating treatment restored 
CHD5 expression. Lower CHD5 mRNA levels correlated with lymph node metastasis (P 
= 0.026). CHD5 protein expression was also reduced in breast cancer, and lack of 
CHD5 expression significantly correlated with higher tumor stage, 
ER/PR-negativity, HER2 positivity, distant metastasis and worse patient survival 
(P ≤ 0.01). Functionally, ectopic expression of CHD5 in breast cancer cells 
inhibited cell proliferation and invasion in vitro and tumorigenesis in nude 
mice. Consistent with the inhibition of invasion, CHD5 down-regulated 
mesenchymal markers vimentin, N-cadherin and ZEB1 in breast cancer cells.
CONCLUSION: Down-regulation of CHD5, mediated at least in part by promoter 
methylation, contributes to the development and progression of human breast 
cancer.