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
en 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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Genes Supresores de Tumor
/
Ritmo Circadiano
/
Carcinoma de Pulmón de Células no Pequeñas
/
Proteínas de Ciclo Celular
/
Silenciador del Gen
/
Neoplasias Pulmonares
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Clin Cancer Res
Asunto de la revista:
NEOPLASIAS
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos