Résumé
Interleukin-17B (IL-17B) is a pro-inflammatory cytokine that belongs to a family encompassing 6 interleukins (IL-17A to F) and binds to the IL-17 receptor B (IL-17RB). Little is known about the potential role of IL-17B/IL-17RB signaling pathway in cancer. Both IL-17B and IL-17RB are up-regulated in breast tumors and are associated with a poor prognosis in patients. We thus focused on their implication in breast cancer. We demonstrated that recombinant IL-17B induces resistance to conventional chemotherapeutic agents such as taxol, an effect that is totally abrogated by disrupting IL-17RB signaling. To further understand the molecular events involved in IL-17B-induced chemoresistance, we focused on signaling pathways activated under stimulation of human breast cancer cell lines by recombinant IL-17B. We observed that IL-17B induces the activation of both ERK1/2 and NFkB pathways, leading to an up-regulation of anti-apoptotic proteins of the Bcl-2 family. Interestingly we showed that the inhibition of ERK1/2 pathway totally prevents IL-17B-induced chemoresistance of breast cancer cell lines. Relevance of these data is currently under investigation in tumor mouse models. Altogether our results demonstrate the implication of the IL-17B/IL-17RB signaling pathway in breast tumors and identify IL-17B and its receptor as potential therapeutic targets for cancer. Citation Format: Emilie Laprevotte, Jeremy Bastid, Stéphanie Cochaud, Jerôme Giustiniani, Marion Philippe, Kathryn A. Frewer, Andrew J. Sanders, Wen G. Jiang, Armand Bensussan, Gilles Alberici, Jean-François Eliaou, Nathalie Bonnefoy. Interleukin-17B promotes chemoresistance of breast tumors through ERK1/2 anti-apoptotic pathway. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5027. doi:10.1158/1538-7445.AM2015-5027