Chk1 as a new therapeutic target in triple-negative breast cancer

Laurence Albiges, Aïcha Goubar, Véronique Scott, Cécile Vicier, Céline Lefèbvre, Samar Alsafadi, Frédéric Commo, Mahasti Saghatchian, Vladimir Lazar, Philippe Dessen, Suzette Delaloge, Fabrice André, Virginie Quidville

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    46 Citations (Scopus)

    Résumé

    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.

    langue originaleAnglais
    Pages (de - à)250-258
    Nombre de pages9
    journalBreast
    Volume23
    Numéro de publication3
    Les DOIs
    étatPublié - 1 janv. 2014

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