title: FOXA1 positively regulates gene expression by changing gene methylation status in human breast cancer MCF-7 cells.
abstract: OBJECTIVE
  DNA methylation is an important epigenetic modification with tumor suppressor gene silencing in cancer. The mechanisms underlying DNA methylation patterns are still poorly understood. This study aims to evaluate the potential value of FOXA1 for controlling gene CpG island methylation in breast cancer.
  
  
  METHODS
  FOXA1 was down-regulated by transfection with siRNA and up-regulated by transfection with plasmid in MCF-7 cell lines. The DNA methylation and mRNA levels were examined by qMSP and qRT-PCR. The cell proliferation and apoptosis was detected by MTT and Flow cytometry.
  
  
  RESULTS
  Suppression of FOXA1 enhanced the methylation status of DAPK, MGMT, RASSF1A, p53, and depressed mRNA levels of these tumor suppressor genes, whereas over-expression of FOXA1 showed the opposite effects. DNMT1, DNMT3A and DNMT3B mRNA were up-regulated by siRNA knock-down of FOXA1. At the same time, FOXA1 suppression promoted cell growth and inhibited apoptosis.
  
  
  CONCLUSIONS
  FOXA1 may be associated with methylation of the tumor suppressor genes promoter through changing DNMTs expression. FOXA1 could be a potential demethylation target for prevention and treatment of breast cancer.
authors.affiliation: Department of General Surgery, The Second Hospital of Anhui Medical University Anhui, Hefei 230601, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of General Surgery, The Second Hospital of Anhui Medical University Anhui, Hefei 230601, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Qian
authors.affiliation: Department of General Surgery, The Second Hospital of Anhui Medical University Anhui, Hefei 230601, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Tian
authors.affiliation: Department of General Surgery, The Second Hospital of Anhui Medical University Anhui, Hefei 230601, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Tang
authors.affiliation: Department of General Surgery, The Second Hospital of Anhui Medical University Anhui, Hefei 230601, China.
authors.forename: Shengyun
authors.initials: S
authors.lastname: Wan
authors.affiliation: Department of General Surgery, The Second Hospital of Anhui Medical University Anhui, Hefei 230601, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Cental Laboratory, The First Hospital of Anhui Medical University Anhui, Hefei 230022, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, The Second Hospital of Anhui Medical University Anhui, Hefei 230601, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Geng
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D019175:DNA Methylation / Q000235:genetics*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
chemical_list: C496499:FOXA1 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha
keywords: FOXA1; MCF-7; methylation; tumor suppressor gene expression