Aberrant DNA methylation links cancer susceptibility locus 15q25.1 to apoptotic regulation and lung cancer.

ABSTRACT: Nicotinic acetylcholine receptor (nAChR) genes form a highly conserved gene cluster at the lung cancer susceptibility locus 15q25.1. In this study, we show that the CHRNalpha3 gene encoding the nAChRalpha3 subunit is a frequent target of aberrant DNA hypermethylation and silencing in lung cancer, whereas the adjacent CHRNbeta4 and CHRNalpha5 genes exhibit moderate and no methylation, respectively. Treatment of cancer cells exhibiting CHRNalpha3 hypermethylation with DNA methylation inhibitors caused demethylation of the CHRNalpha3 promoter and gene reactivation. Restoring CHRNalpha3 levels through ectopic expression induced apoptotic cell death. Small hairpin RNA-mediated depletion of nAChRalpha3 in CHRNalpha3-expressing lung cancer cells elicited a dramatic Ca(2+) influx response in the p

SUBMITTER: Paliwal A 

PROVIDER: S-EPMC2856323 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature