Table of Contents Author Guidelines Submit a Manuscript
International Journal of Breast Cancer
Volume 2011 (2011), Article ID 912102, 9 pages
Review Article

The Role of Interferon Regulatory Factor-1 (IRF1) in Overcoming Antiestrogen Resistance in the Treatment of Breast Cancer

Georgetown University Medical Center, W401 Research Building, 3970 Reservoir Road, NW, Washington, DC 20057, USA

Received 18 February 2011; Revised 29 April 2011; Accepted 9 May 2011

Academic Editor: Chengfeng Yang

Copyright © 2011 J. L. Schwartz et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Resistance to endocrine therapy is common among breast cancer patients with estrogen receptor alpha-positive (ER+) tumors and limits the success of this therapeutic strategy. While the mechanisms that regulate endocrine responsiveness and cell fate are not fully understood, interferon regulatory factor-1 (IRF1) is strongly implicated as a key regulatory node in the underlying signaling network. IRF1 is a tumor suppressor that mediates cell fate by facilitating apoptosis and can do so with or without functional p53. Expression of IRF1 is downregulated in endocrine-resistant breast cancer cells, protecting these cells from IRF1-induced inhibition of proliferation and/or induction of cell death. Nonetheless, when IRF1 expression is induced following IFNγ treatment, antiestrogen sensitivity is restored by a process that includes the inhibition of prosurvival BCL2 family members and caspase activation. These data suggest that a combination of endocrine therapy and compounds that effectively induce IRF1 expression may be useful for the treatment of many ER+ breast cancers. By understanding IRF1 signaling in the context of endocrine responsiveness, we may be able to develop novel therapeutic strategies and better predict how patients will respond to endocrine therapy.