Chk1 as a new therapeutic target in triple-negative breast cancer.
Breast
; 23(3): 250-8, 2014 Jun.
Article
en En
| MEDLINE
| ID: mdl-24636978
OBJECTIVES: Bioinformatics analyses of pathways and genes differentially expressed between malignant and benign lesions could allow discovering new therapeutic targets. Here, we identified Checkpoint kinase 1 (Chk1) as a potent therapeutic target in triple-negative breast cancer (TNBC). MATERIALS AND METHODS: Differential gene expression between TNBC, other malignant and benign lesions was performed on two breast cancer datasets. Chk1 was targeted using RNA interference or chemical inhibitor in several TNBC cell lines. RESULTS: DNA repair pathway was identified as one mostly deregulated pathway in TNBC as compared to benign lesions. Chk1 was identified as candidate target among the 35 genes included in this pathway. Gene expression analysis revealed that Chk1 gene was significantly overexpressed in TNBC as compared to non-TNBC and benign lesions. Depletion of Chk1 protein expression induced a marked reduction of cell viability and led to mitotic catastrophe in TNBC cells. Chemical Chk1 inhibitor decreased survival in TNBC cells, and transcriptome analyze revealed a modulation of gene expression profile in response to Chk1 treatment. CONCLUSION: These findings suggest that Chk1 may represent a therapeutic target in TNBC, and provide a rationale to evaluate Chk1 inhibitors in breast cancer patients.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Quinasas
/
Inhibidores de Proteínas Quinasas
/
Neoplasias de la Mama Triple Negativas
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Breast
Asunto de la revista:
ENDOCRINOLOGIA
/
NEOPLASIAS
Año:
2014
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Países Bajos