Xeroderma pigmentosum group C gene expression is predominantly regulated by promoter hypermethylation and contributes to p53 mutation in lung cancers

摘要: Reduced DNA repair capability is associated with developing lung cancer, especially in nonsmokers. XPC participates the initial recognition of damage during nucleotide excision process. We hypothesize that inactivation by promoter hypermethylation may play an important role reduction to cause p53 mutation carcinogenesis. In this report we demonstrate 17 CpG islands between −175 and −1 correlates very well expression levels eight cancer cell lines. When cells hypermethylated promoters were treated demethylating agent 5-aza-2′-deoxycytidine, was de-repressed. Interestingly, found 4 5 (80%) lines harbored mutation, but not observed two which had a wild-type gene. Among analysis status 158 tumors, more common nonsmokers (39 94, 41%) than smokers (14 64, 22%; P=0.010). Additionally, often G → T or C mutations To verify whether involved occurrence gene A549 knockdown small interference RNA then XPC-inactivated benzo[a]pynrene for different passages. Surprisingly, at codon 215 indeed detected passages 15 confirmed loss transcription activity mdm2. These results show crucial inactivation, partly contribute tumorigenesis,