Epigenetic silencing of the candidate tumor suppressor gene Per1 in non-small cell lung cancer.
Clin Cancer Res
; 13(5): 1399-404, 2007 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-17332281
ABSTRACT
PURPOSE:
Epigenetic events are a critical factor contributing to cancer development. The purpose of this study was to identify tumor suppressor genes silenced by DNA methylation and histone deacetylation in non-small cell lung cancer (NSCLC). EXPERIMENTALDESIGN:
We used microarray analysis to screen for tumor suppressor genes.RESULTS:
We identified Per1, a core circadian gene, as a candidate tumor suppressor in lung cancer. Although Per1 levels were high in normal lung, its expression was low in a large panel of NSCLC patient samples and cell lines. Forced expression of Per1 in NSCLC cell lines led to significant growth reduction and loss of clonogenic survival. Recent studies showed that epigenetic regulation, particularly histone H3 acetylation, is essential for circadian function. Using bisulfite sequencing and chromatin immunoprecipitation, we found that DNA hypermethylation and histone H3 acetylation are potential mechanisms for silencing Per1 expression NSCLC.CONCLUSIONS:
These results support the hypothesis that disruption of circadian rhythms plays an important role in lung tumorigenesis. Moreover, our findings suggest a novel link between circadian epigenetic regulation and cancer development.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Genes Supressores de Tumor
/
Ritmo Circadiano
/
Carcinoma Pulmonar de Células não Pequenas
/
Proteínas de Ciclo Celular
/
Inativação Gênica
/
Neoplasias Pulmonares
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Clin Cancer Res
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos