Modulation of claudin-1 expression by ∆2-TGZ in triple negative breast cancer cells is correlated to apoptosis - Archive ouverte HAL Accéder directement au contenu
Communication Dans Un Congrès Année : 2017

Modulation of claudin-1 expression by ∆2-TGZ in triple negative breast cancer cells is correlated to apoptosis

Résumé

Breast cancer represents the second lethal malignancy across the world. Efficient targeted therapies can be used in presence of the molecular biomarkers ER, PR and HER2. Nevertheless, these therapies are ineffective on triple negative breast cancer (ER-, PR- and HER2-). Furthermore, 40% of triple negative tumors do not express claudin-1, a major constituent of tight junction. These tumors present a higher relapse incidence. A major challenge in oncology is the development of innovative therapies for these poor prognosis tumors. In this context, we study the anticancer effects of thiazolidinediones (TZD). We develop ∆2-TGZ a compound derived from troglitazone (TGZ), which presents an improved anti-proliferative activity and a lower hepatic toxicity than the parent molecule. We showed by DNA microarray that claudin-1 is the most expressed gene in response to ∆2-TGZ treatment in MCF-7 breast cancer cells. The aim of our work is to determine if claudin-1 contributes to the pro-apoptotic effect of ∆2-TGZ. In the present study, we demonstrated that ∆2-TGZ induces apoptosis and claudin-1 protein expression in MDA-MB-231 and Hs578T “claudin 1-low” triple negative cells, but not in the non-tumorigenic human breast epithelial cell line MCF-10A. Furthermore, we showed that claudin-1 overexpression plays an important role in apoptosis in MDA-MB-231 and Hs578T cells. Concerning ∆2-TGZ-induced apoptosis, we showed that claudin-1 is involved in MDA-MB-231 cells but not in Hs578T cells suggesting a different mechanism of action. In conclusion, these data consolidate our hypothesis that claudin-1 is involved in the pro-apoptotic process in MDA-MB-231 and Hs578T cells. In fine, our study suggests that the strategy of claudin-1 re-expression could be a promising therapeutic option for the aggressive “claudin 1-low” triple negative subtype.

Domaines

Cancer
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Dates et versions

hal-01665256 , version 1 (15-12-2017)

Identifiants

  • HAL Id : hal-01665256 , version 1

Citer

Marine Geoffroy, Alexandra Kleinclauss, Michel Boisbrun, Stéphane Flament, Sandra Kuntz, et al.. Modulation of claudin-1 expression by ∆2-TGZ in triple negative breast cancer cells is correlated to apoptosis. 2nd EACR-OECI Conference Making it Personal - Cancer Precision Medicine, Mar 2017, Amsterdam, Netherlands. ⟨hal-01665256⟩
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