Abstract 79: Overexpression of BQ323636.1 modulates tamoxifen resistance in ER positive breast cancer via IL-8-mediated signaling pathway

Abstract

Abstract Background Tamoxifen has been used as first-line adjuvant treatment for estrogen receptor positive (ER+) breast cancer; however, the development of acquired resistance compromises its efficacy. Previously, our group identified BQ323636.1(BQ), a novel splice variant of nuclear receptor repressor 2 (NCOR2), which confers tamoxifen resistance by enhancing ER transcriptional activity1, 2. We hypothesize that BQ may also modulate tamoxifen resistance via androgen receptor (AR) activity. The current study investigates the effect of BQ in modulating the activities of ER and AR in tamoxifen resistant breast cancer. Methods In silico search was employed to identify candidate genes that contained both the androgen responsive element (ARE) and estrogen responsive element (ERE) genome-wide. Expression of candidate genes were evaluated by RT-qPCR. Western blot was used to determine the protein expression. Stably transfected BQ overexpressing MCF7 cell line (MCF7-BQ) and control cell line (MCF7-His) were established. ELISA was employed to determine the amount of IL-8. Repertaxin was used to inhibit IL-8 mediated signaling pathway. Results There were 22 candidate genes identified by in silico search. qPCR confirmed that IL-8 gene contained both functional ERE and ARE in MCF-7 cells. Overexpression of BQ could enhance the expression of IL-8 at both mRNA and protein levels. ELISA assay confirmed that BQ overexpression could promote the secretion of IL-8 in breast cancer cells. Western blot analysis showed that BQ overexpression could not alter the expression of IL-8 receptor CXCR1. The treatment with repertaxin could recover the response of MCF7-BQ to tamoxifen. Conclusions Our results suggest that BQ323636.1 could up-regulate IL-8 to modulate tamoxifen resistance. Targeting IL-8 signaling may provide insights to overcome tamoxifen resistance in ER+ breast cancer.