title: Aberrant NDRG1 methylation associated with its decreased expression and clinicopathological significance in breast cancer.
abstract: BACKGROUND
  Cancer cell differentiation is an important characteristic of malignant tumor and has a great impact on prognosis and therapeutic decision for patients. The N-myc downstream regulated gene 1 (NDRG1), a putative tumor suppression gene, is involved in the regulation of human cell differentiation and metastasis in various cancers. Changes in the status of methylation of the NDRG1 gene have not been studied in detail in human breast cancer.
  
  
  RESULTS
  The MDA-MB-231 breast tumor cell line could express NDRG1. However, it was only expressed after treatment with 5-Aza-2'-deoxycytidine (AZA) in T47D cell line, which revealed that NDRG1 expression could modulated by DNA methylation. Therefore, the fragment surrounding the transcript start site of NDRG1 gene promoter was cloned after sodium bisulfite DNA treatment. A high density (66%) of methylation for human NDRG1 gene promoter was detected in T47D; however, there was only 16% of methylated CpG dinucleotides in the NDRG1 gene promoter in MDA-MB-231. DNA methylation in the NDRG1 promoter was detected in 31.1% of primary breast cancer samples. Furthermore, the NDRG1 promoter methylation correlated with the Tumor Node Metastasis (TNM) at stage III/IV, metastasis, lymph invasion, moderate and poor histological grade in the breast cancer patients.
  
  
  CONCLUSIONS
  These findings suggest that the DNA methylation status of NDRG1 gene may play an important role in the pathogenesis and/or development of breast cancer, and the expression could be regulated by aberrant DNA methylation.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College, Qingdao University, Qingdao 266021, China. qdqyhl@126.com
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Han
authors.forename: Lin
authors.initials: L
authors.lastname: Hou
authors.forename: Ming-Jin
authors.initials: MJ
authors.lastname: Zhou
authors.forename: Zhong-liang
authors.initials: ZL
authors.lastname: Ma
authors.forename: Dong-Liang
authors.initials: DL
authors.lastname: Lin
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.forename: Yin-lin
authors.initials: YL
authors.lastname: Ge
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000187:drug effects / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects / Q000276:immunology*; D000077209:Decitabine; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D001374:Azacitidine; D018797:Cell Cycle Proteins; D000077209:Decitabine; D047908:Intracellular Signaling Peptides and Proteins; D000099259:N-myc Downstream-Regulated Gene 1 Protein
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