title: Estrogen receptor β promoter methylation: a potential indicator of malignant changes in breast cancer.
abstract: BACKGROUND
  Estrogen receptor β (ERβ) always lacks expression in estrogen-dependent tumors, which may result from gene inactivation by methylation. In this study, we aimed to determine whether aberrant methylation of the ERβ promoter is associated with decreased ERβ gene expression in breast cancer.
  
  
  METHODS
  ERβ methylation status was determined for 132 pairs of breast cancer and adjacent normal tissues via the MethyLight method. Additionally, mRNA relative expression was quantified by real-time polymerase chain reaction (RT-PCR) to determine whether aberrant methylation had a negative correlation with expression. The correlation of ERβ promoter methylation and clinical parameters is also discussed.
  
  
  RESULTS
  Methylation was observed in 96 (72.7%) breast cancer samples, and the median percentage of fully methylated reference (PMR) among methylated tissues was 0.83. Meanwhile, 94 (71.2%) adjacent normal tissues were methylated and the median PMR was 0.48. Compared to adjacent normal tissues, the methylation level of breast cancer was significantly higher (p < 0.001) and mRNA expression was much lower (p < 0.001). There was a significant correlation between ERβ methylation and mRNA expression in adjacent normal breast tissues (p = 0.004). In addition, the methylation rate of cancer tissues whose maximum diameter < 3 cm was significantly higher than those > 3 cm (p = 0.025).
  
  
  CONCLUSIONS
  ERβ promoter methylation level varies between cancerous and adjacent normal breast tissues. There was significant downregulation of ERβ methylation expression in pre-cancerous stages of breast cancer. Therefore, demethylation drugs may offer a potential strategy for preventing the development of pre-cancerous cells.
authors.affiliation: Laboratory Department, GuangAn'men Hospital, China Academy of Chinese Medical Sciences, Beijing, China; Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital University of Medical Sciences, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Qi
authors.affiliation: Department of Oncology, Dongfang Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Kaiwen
authors.initials: K
authors.lastname: Hu
authors.affiliation: Laboratory Department, GuangAn'men Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Ruili
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Laboratory Department, GuangAn'men Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Shipeng
authors.initials: S
authors.lastname: Sun
authors.affiliation: Anyang Cancer Hospital, Anyang, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Laboratory Department, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Ximing
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Oncology, GuangAn'men Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Baojin
authors.initials: B
authors.lastname: Hua
authors.affiliation: Laboratory Department, GuangAn'men Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Guijian
authors.initials: G
authors.lastname: Liu
keywords: breast cancer; estrogen receptor β; methylation; percentage of fully methylated reference