IL-1-conferred gene expression pattern in ERα+ BCa and AR+ PCa cells is intrinsic to ERα− BCa and AR− PCa cells and promotes cell survival

作者：Afshan F. Nawas, Mohammed Kanchwala, Shayna Thomas-Jardin, Haley Dahl, Kelly Daescu, Monica Bautista, Vanessa Anunobi, Ally Wong, Rachel K. Meade, Ragini M. Mistry, Nisha Ghatwai, Felix Bayerl, Chao Xing, Nikkí A. Delk · 发表于：BMC Cancer · 年份：2020 · DOI：10.1186/s12885-020-6529-9 · 被引用次数：18 · 研究领域：Cancer Immunotherapy and Biomarkers、Inflammatory mediators and NSAID effects、Cytokine Signaling Pathways and Interactions

Abstract Background Breast (BCa) and prostate (PCa) cancers are hormone receptor (HR)-driven cancers. Thus, BCa and PCa patients are given therapies that reduce hormone levels or directly block HR activity; but most patients eventually develop treatment resistance. We have previously reported that interleukin-1 (IL-1) inflammatory cytokine downregulates ERα and AR mRNA in HR-positive (HR + ) BCa and PCa cell lines, yet the cells can remain viable. Additionally, we identified pro-survival proteins and processes upregulated by IL-1 in HR + BCa and PCa cells, that are basally high in HR − BCa and PCa cells. Therefore, we hypothesize that IL-1 confers a conserved gene expression pattern in HR + BCa and PCa cells that mimics conserved basal gene expression patterns in HR − BCa and PCa cells to promote HR-independent survival and tumorigenicity. Methods We performed RNA sequencing (RNA-seq) for HR + BCa and PCa cell lines exposed to IL-1 and for untreated HR − BCa and PCa cell lines. We confirmed expression patterns of select genes by RT-qPCR and used siRNA and/or drug inhibition to silence select genes in the BCa and PCa cell lines. Finally, we performed Ingenuity Pathway Analysis (IPA) and used the gene ontology web-based tool, GOrilla, to identify signaling pathways encoded by our RNA-seq data set. Results We identified 350 genes in common between BCa and PCa cells that are induced or repressed by IL-1 in HR + cells that are, respectively, basally high or low in HR − cells. Amon...