Mechanisms underlying lack of insulin-like growth factor-binding protein-3 expression in non-small-cell lung cancer

摘要: Expression of insulin-like growth factor-binding protein-3, which (IGFBP-3) inhibits the proliferation non-small-cell lung cancer (NSCLC) cells by inducing apoptosis, is lost in about half stage I NSCLC cases. Since promoter methylation can silence gene expression, we investigated whether hypermethylation IGFBP-3 involved loss expression NSCLC. We found to be methylated seven 13 cell lines and 16 23, 9, eight 11, six tumor specimens from patients with I, II, III, IV NSCLC, respectively. Methylation status correlated mRNA protein levels a subset tested our study. However, treatment 5'-aza-2'-deoxycytidine (5'-aza-dC) restored four promoter, suggesting that multiple mechanisms regulate Gel shift chromatin immunoprecipitation assays showed Sp-1/Sp-3-binding element influenced binding Sp-1, methyl-CpG-binding protein-2 (MeCP2), histone deacetylase (HDAC). A luciferase construct expressing Sp-1/Sp-3 was significantly reduced transcriptional activity. The reduction activity further suppressed overexpression MeCP2, rescued 5'-aza-dC. Thus interference Sp-1 transactivation MeCP2 may contribute defect promoter.