title: Aberrant Hypermethylation at Sites -86 to 226 of DAB2 Gene in Non-Small Cell Lung Cancer.
abstract: BACKGROUND
  Lung cancer is now the leading cause of malignant tumor-related deaths worldwide and non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases. Human Disabled-2 (DAB2) was reported to act as a tumor suppressor gene and was found downregulated in numerous cancer types. However, the expression of DAB2 in NSCLC and the mechanism of DAB2 expression regulation remain unclear.
  
  
  METHODS
  DAB2 expression was analyzed by quantitative real-time polymerase chain reaction (PCR) and Western blot in 20 paired primary NSCLC tissues and corresponding normal lung tissues. Immunohistochemistry assay was performed in paired NSCLC tissues from another 20 patients. Methylation status of DAB2 promoter was analyzed using bisulfite sequencing polymerase chain reaction.
  
  
  RESULTS
  DAB2 messenger RNA level was significantly lower in NSCLC tissues than normal tissues in 95.0% of the group of patients under investigation. In addition, NSCLC tissues showed a significant reduction in DAB2 protein when compared with normal tissues. Importantly, 85% of NSCLC tissues (17/20) had high methylation in DAB2 promoter when compared with normal tissues.
  
  
  CONCLUSIONS
  DAB2 expression is decreased in NSCLC, and the frequent methylation event at sites -86 to 226 of the DAB2 gene could contribute to the downregulation of DAB2.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery (CL, JC, TC, ZX, CX, CD, YW, JZ), the First Affiliated Hospital of Soochow University, Medical College of Soochow University, Suzhou, China; Soochow University Laboratory of Cancer Molecular Genetics (CL, ZL, H-TZ, JZ), Medical College of Soochow University, Suzhou, China; and Suzhou Key Laboratory for Cancer Molecular Genetics (CL, ZL, H-TZ, JZ), Suzhou, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Tengfei
authors.initials: T
authors.lastname: Chen
authors.forename: Zhenlei
authors.initials: Z
authors.lastname: Xu
authors.forename: Chun
authors.initials: C
authors.lastname: Xu
authors.forename: Cheng
authors.initials: C
authors.lastname: Ding
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhe
authors.initials: Z
authors.lastname: Lei
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D051017:Apoptosis Regulatory Proteins; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008168:Lung / Q000473:pathology*; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger; D015398:Signal Transduction / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C102885:DAB2 protein, human; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins