IRF1 promotes antiestrogen sensitivity by regulating Bik expression in breast cancer cells

Antiestrogen have long been the standard treatment for ER+ breast cancer patients. However, antiestrogen resistance, either de novo or acquired, is a major hurdle for effective therapy in breast cancer patients. To address this, the underlying mechanisms of antiestrogen resistance must be understood. Antiestrogens are known to induce apoptosis in sensitive breast cancer cells. The screening of anti‐apoptotic genes indicates that BH3‐only genes Bik, Bmf, and Bid are strongly induced by antiestrogen in sensitive cells. In contrary, this robust induction is lost in resistant cells. Our previous finding indicates that the down‐regulation of IRF1 mediates antiestrogen resistance in breast cancer cells. In this study, we tested whether IRF1 promotes antiestrogen sensitivity by inducing the BH3‐only genes. We show that overexpressed IRF1 promotes the expression of Bik at basal conditions at both mRNA and protein level. Inhibition of IRF1 transcriptional activity by overepxressing a dominant negative form of IRF1 prevents the induction of Bik in Fulvestrant exposed sensitive cells. Our data further suggest that the IRF1‐mediated regulation is achieved at the transcriptional level. In summary, our finding indicates that IRF1 mediates the antiestrogen induced Bik expression in breast cancer cells.