title: Chromodomain helicase DNA binding protein 5 plays a tumor suppressor role in human breast cancer.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  Down-regulation of CHD5, mediated at least in part by promoter methylation, contributes to the development and progression of human breast cancer.
authors.affiliation: Department of Genetics and Cell Biology, Nankai University College of Life Sciences, 94 Weijin Road, Tianjin 300071, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wu
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Zhu
authors.forename: Weidong
authors.initials: W
authors.lastname: Li
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Fu
authors.forename: Dan
authors.initials: D
authors.lastname: Su
authors.forename: Liya
authors.initials: L
authors.lastname: Fu
authors.forename: Zhiqian
authors.initials: Z
authors.lastname: Zhang
authors.forename: Ang
authors.initials: A
authors.lastname: Luo
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Sun
authors.forename: Li
authors.initials: L
authors.lastname: Fu
authors.forename: Jin-Tang
authors.initials: JT
authors.lastname: Dong
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D018899:CpG Islands; D056915:DNA Copy Number Variations; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism*; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D015820:Cadherins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D014746:Vimentin; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D004265:DNA Helicases; C471926:CHD5 protein, human