Identification and functional analysis of interleukin-1 (IL-1) induced gene expression pattern in breast cancer (BCa) and prostate cancer (PCa) cells

Breast cancer (BCa) and prostate cancer (PCa) are both hormone receptor (HR) driven cancers with similar etiology, where tumor microenvironment inflammation promotes both BCa and PCa progression. Interleukin-1 (IL-1) is an inflammatory cytokine present in the tumor microenvironment, is elevated in BCa and PCa patient tumor tissue, correlates with poor prognosis, and inversely correlates with HR expression in tumor tissue. We have shown that IL-1 represses the BCa and PCa therapeutic targets, Estrogen Receptor Alpha (ERα) and Androgen Receptor (AR), respectively, in PCa and BCa cell lines; yet the cells remain viable. Thus, we hypothesize that IL-1 induces similar molecular responses in BCa and PCa cells that promote HR independence and subsequent treatment resistance. To address our hypothesis, we performed RNA sequencing of HR positive (HR+) BCa and PCa cell lines treated with IL-1 and compared IL-1-modulated gene expression patterns with the basal gene expression of HR negative (HR-) BCa and PCa cell lines. Our bioinformatics analysis revealed a suite of 350 genes that, based on ontology, promote inflammation response, angiogenesis, oxidative stress response, and cell motility. We chose two IL-1-induced genes from the genes list, p62 and SOX9, for functional analysis. p62 is an antioxidant and autophagy-related scaffold protein and SOX9 is an embryonic transcription factor. We performed p62 and SOX9 siRNA and found that loss of p62 or SOX9 reduce cell viability in HR- cell lines. We also found that the FDA approved p62-targeting drug, verteporfin, reduces cell viability in HR- cells line. Thus, our 350 genes list revealed alternative therapeutic targets for HR-independent cells, including BCa or PCa patients that might evolve HR-independence due to inflammation. Citation Format: Afshan Fathima Nawas, Mohammed Kanchwala, Shayna Thomas-Jardin, Haley Dahl, Nicole Roos, Monica Bautista, Ally Wong, Chao Xing, Nikki Delk. Identification and functional analysis of interleukin-1 (IL-1) induced gene expression pattern in breast cancer (BCa) and prostate cancer (PCa) cells [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-07-09.