The Role of Interferon Regulatory Factor-1 (IRF1) in Overcoming Antiestrogen Resistance in the Treatment of Breast Cancer
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 fac...
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | International Journal of Breast Cancer |
| Online Access: | http://dx.doi.org/10.4061/2011/912102 |
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| author | J. L. Schwartz A. N. Shajahan R. Clarke |
| author_facet | J. L. Schwartz A. N. Shajahan R. Clarke |
| author_sort | J. L. Schwartz |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ee989cb9210141e2a92f21409c6668a2 |
| institution | Kabale University |
| issn | 2090-3189 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Breast Cancer |
| spelling | doaj-art-ee989cb9210141e2a92f21409c6668a22025-02-03T01:11:16ZengWileyInternational Journal of Breast Cancer2090-31892011-01-01201110.4061/2011/912102912102The Role of Interferon Regulatory Factor-1 (IRF1) in Overcoming Antiestrogen Resistance in the Treatment of Breast CancerJ. L. Schwartz0A. N. Shajahan1R. Clarke2Georgetown University Medical Center, W401 Research Building, 3970 Reservoir Road, NW, Washington, DC 20057, USAGeorgetown University Medical Center, W401 Research Building, 3970 Reservoir Road, NW, Washington, DC 20057, USAGeorgetown University Medical Center, W401 Research Building, 3970 Reservoir Road, NW, Washington, DC 20057, USAResistance 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.http://dx.doi.org/10.4061/2011/912102 |
| spellingShingle | J. L. Schwartz A. N. Shajahan R. Clarke The Role of Interferon Regulatory Factor-1 (IRF1) in Overcoming Antiestrogen Resistance in the Treatment of Breast Cancer International Journal of Breast Cancer |
| title | The Role of Interferon Regulatory Factor-1 (IRF1) in Overcoming Antiestrogen Resistance in the Treatment of Breast Cancer |
| title_full | The Role of Interferon Regulatory Factor-1 (IRF1) in Overcoming Antiestrogen Resistance in the Treatment of Breast Cancer |
| title_fullStr | The Role of Interferon Regulatory Factor-1 (IRF1) in Overcoming Antiestrogen Resistance in the Treatment of Breast Cancer |
| title_full_unstemmed | The Role of Interferon Regulatory Factor-1 (IRF1) in Overcoming Antiestrogen Resistance in the Treatment of Breast Cancer |
| title_short | The Role of Interferon Regulatory Factor-1 (IRF1) in Overcoming Antiestrogen Resistance in the Treatment of Breast Cancer |
| title_sort | role of interferon regulatory factor 1 irf1 in overcoming antiestrogen resistance in the treatment of breast cancer |
| url | http://dx.doi.org/10.4061/2011/912102 |
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