Fiche publication


Date publication

janvier 2015

Auteurs

Membres identifiés du Cancéropôle Est :
Dr GARBAR Christian , Pr MERROUCHE Yacine , Pr ANTONICELLI Franck , Pr BENSUSSAN Armand


Tous les auteurs :
Mombelli S, Cochaud S, Merrouche Y, Garbar C, Antonicelli F, Laprevotte E, Alberici G, Bonnefoy N, Eliaou JF, Bastid J, Bensussan A, Giustiniani J

Résumé

Pro-inflammatory IL-17 cytokines were initially described for their pathogenic role in chronic inflammatory diseases and subsequent accumulating evidence indicated their involvement in carcinogenesis. In the present study we report that IL-17A and IL-17E receptors subunits mRNA expressions are upregulated in breast cancers versus normal samples. IL-17E, which is undetectable in most normal breast tissues tested, seems more expressed in some tumors. Investigation of the molecular signaling following stimulation of human breast cancer cell lines with IL-17A and IL-17E showed that both cytokines induced the phosphorylation of c-RAF, ERK1/2 and p70 S6 Kinase were involved in the proliferation and survival of tumor cells. Accordingly, IL-17A and IL-17E promoted resistance to Docetaxel and failed to induce apoptosis as previously reported for IL-17E. Interestingly, we also revealed that both cytokines induced the generation of tumorogenic low molecular weight forms of cyclin E (LMW-E), which high levels correlated strongly with a poor survival in breast cancer patients. These results show for the first time some of the molecular pathways activated by IL-17A and IL-17E that may participate to their pro-oncogenic activity in breast cancers.

Référence

Sci Rep. 2015 Jul 8;5:11874