Il-25/Il-17e Does Not Induce Breast Tumor Cell Apoptosis And Both Il-17a And Il-25/Il-17e Contribute To Breast Cancer Survival And Proliferation Associated With Generation Of Pro-Oncogenic Low Molecular Forms Of Cyclin E

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 focused our work on IL-17A and IL-17E which are found in the breast tumoral microenvironment. Cell proliferation and cytotoxic assays as well as Quantitative PCR and Western Blot analysis of oncogenic pathways were performed using several breast cancer cell lines and primary tumor cells. We report that IL-17A and IL-17E receptor subunits (IL17RA, RB and RC chains) are up-regulated in breast cancers versus normal samples. Moreover, IL-17E, which is undetectable in most normal breast tissues tested, is expressed at higher levels in tumors. We studied the molecular signaling following the stimulation of cell lines with IL-17A and IL-17E. We found that both cytokines induced cell proliferation and activation of pathways involved in cells survival. Accordingly, IL-17A and IL-17E promoted resistance to Docetaxel but failed to induce apoptosis as previously reported for IL-17E. Interestingly, we also revealed that both cytokines induced the generation of tumorigenic low molecular weight forms of cyclin E (LMW-E), high levels of which correlate 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. Citation Format: Jerome Giustiniani, Herve Cure, Christian Garbar, Yacine Merrouche, Nathalie Bonnefoy, Jeremy Bastid, Gilles Alberici, Jean-Francois Eliaou, Armand Bensussan. IL-25/IL-17E does not induce breast tumor cell apoptosis and both IL-17A and IL-25/IL-17E contribute to breast cancer survival and proliferation associated with generation of pro-oncogenic low molecular forms of cyclin E. [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 3171. doi:10.1158/1538-7445.AM2015-3171