Transcription factors (TFs) are direct effectors of altered signaling pathways in cancer. To uncover new TFs that would determine clinical outcomes in breast cancer patients, we systematically analyzed gene expression data from breast cancer patients. Our results revealed that forkhead box protein M1 (FOXM1) is the top-ranked survival-associated TF with triple-negative breast cancer. Surprisingly, silencing FOXM1 expression led breast cancer cells to become more sensitive to doxorubicin (Dox). We found that FOXM1-dependent resistance to Dox is mediated by regulating DNA repair genes. We further demonstrated that NF-κB1 interacts with FOXM1 in the presence of Dox to protect breast cancer cells from DNA damage. Finally, silencing FOXM1 expression in a mouse xenograft model significantly sensitized the cells to Dox. Our systematic approaches identified an unexpected role of FOXM1 in Dox resistance by regulating DNA repair genes and FOXM1 may be a promising therapeutic target for sensitizing breast cancer cells to Dox.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2962. doi:1538-7445.AM2012-2962