title: [Promoter methylation of ASPP1 and ASPP2 genes in non-small cell lung cancers].
abstract: OBJECTIVE
  To investigate the methylation status of CpG islands in the promoter region and the protein expression of ASPP1 and ASPP2 genes in non-small-cell lung cancer (NSCLC) and their relationship with cellular apoptosis and p53 gene expression.
  
  
  METHODS
  The 5'CpG island methylation patterns of ASPP1 and ASPP2 were evaluated by methylation specific polymerase chain reaction (MSP) followed by confirmation of sequencing. Immunohistochemistry was used to detect the expression of ASPP1, ASPP2 and p53 in lung carcinoma tissue samples (n = 90) and adjacent non-neoplastic lung tissue samples (n = 25). TUNEL assay was used to detect the apoptotic activity.
  
  
  RESULTS
  The presence of ASPP1 methylation was significantly higher in NSCLC than that in the adjacent non-neoplastic lung tissue [42.2% (38/90) vs. 16.0% (4/25), P = 0.019]. ASPP1 promoter methylation had a close relationship with TNM stage and lymph node metastasis (P = 0.031, P = 0.030), but was not related to the age, sex, histological types and the grades of tumor differentiation (P = 0.389, P = 0.278, P = 0.570, and P = 0.103). Tumors with ASPP1 promoter methylation demonstrated a lower expression of ASPP1 as compared with those without the methylation (P = 0.002). ASPP1 expression was associated with a higher apoptotic index (AI) (P = 0.022) and a decreased p53 expression (r = -0.259, P < 0.01). Methylation in the promoter region of ASPP2 gene was not detected in lung cancer (n = 90) or adjacent non-neoplastic lung tissue (n = 25). Expression of ASPP2 protein did not correlate with AI (P = 0.282) and p53 status in NSCLC.
  
  
  CONCLUSIONS
  High methylation of ASPP1 gene promoter regions is one of the important mechanisms that down-regulate its protein expression in NSCLC. ASPP1 promoter methylation may be associated with the malignant progression of the tumor, and ASPP1 expression promotes cellular apoptosis.
authors.affiliation: Department of Pathology, Kunming Medical College, Kunming, China. wei_wanli@163.com
authors.forename: Wan-li
authors.initials: WL
authors.lastname: Wei
authors.forename: Hong-yan
authors.initials: HY
authors.lastname: Hu
authors.forename: Li-juan
authors.initials: LJ
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.forename: En
authors.initials: E
authors.lastname: Ye
authors.forename: Xiao-fang
authors.initials: XF
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C498406:PPP1R13B protein, human; C495901:TP53 protein, human; C090468:TP53BP2 protein, human; D016159:Tumor Suppressor Protein p53