Chip-seq analysis of H3K4me3, H3K27me3, DNMT1 and EZH2 binding to chromatin following acute (10 days) and chronic (10 months) treatment of human bronchial epithelial cells (HBEC3KT) cells with 10 µg/ml cigarette smoke condensate (CSC).

ABSTRACT: We define how chronic cigarette smoke-induced time-dependent epigenetic alterations can sensitize human bronchial epithelial cells (HBEC) for transformation by a single oncogene. The smoke-induced, chromatin changes include initial repressive polycomb marking of genes later manifesting abnormal DNA methylation by 10 months. At this time, cells manifest epithelial to mesenchymal changes, anchorage-independent growth and upregulated RAS/MAPK signaling with silencing of hyper-methylated genes normally inhibiting these pathways and which are associated with smoking related NSCLC. These cells, in the absence of any driver gene mutations, now transform by introducing a single KRAS mutation and form adeno-squamous lung carcinomas in mice. Thus, epigenetic abnormalities may prime for changing oncogene senescence to addiction for a single key oncogene involved in lung cancer initiation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE103331 | GEO | 2017/10/21

SECONDARY ACCESSION(S): PRJNA401848

REPOSITORIES: GEO