The Role of Interferon Regulatory Factor-1 (IRF1) in Overcoming Antiestrogen Resistance in the Treatment of Breast Cancer
نویسندگان
چکیده
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.
منابع مشابه
IFNgamma restores breast cancer sensitivity to fulvestrant by regulating STAT1, IFN regulatory factor 1, NF-kappaB, BCL2 family members, and signaling to caspase-dependent apoptosis.
Antiestrogens are effective therapies for the management of many estrogen receptor-alpha (ER)-positive breast cancers. Nonetheless, both de novo and acquired resistance occur and remain major problems in the clinical setting. IFNgamma is an inflammatory cytokine that induces the expression and function of IFN regulatory factor 1 (IRF1), a tumor suppressor gene that can increase antiestrogen res...
متن کاملInterferon regulatory factor-1 signaling regulates the switch between autophagy and apoptosis to determine breast cancer cell fate.
Interferon regulatory factor-1 (IRF1) is a tumor suppressor that regulates cell fate in several cell types. Here, we report an inverse correlation in expression of nuclear IRF1 and the autophagy regulator ATG7 in human breast cancer cells that directly affects their cell fate. In mice harboring mutant Atg7, nuclear IRF1 was increased in mammary tumors, spleen, and kidney. Mechanistic investigat...
متن کاملInterferon Regulatory Factor-1 (irf1) Signaling Regulates Apoptosis and Autophagy to Determine Endocrine Responsiveness and Cell Fate in Human Breast Cancer
متن کامل
Concomitant Increase of OX40 and FOXP3 Transcripts in Peripheral Blood of Patients with Breast Cancer
Background: Regulatory T cells (T-regs) have an important role in cancer by suppression of protective antitumor immune responses. Regulatory T cells express the forkhead/winged helix transcription factor (FOXP3) and OX40 molecules which have important regulatory roles in the immune system. Objective: To evaluate FOXP3 and OX40 transcripts in the peripheral blood mononuclear cells of women with ...
متن کاملبررسی بیوانفورماتیکی میانکنش بین میکرو RNAها با ژن‌های دخیل در عود مجدد سرطان پستان درمان شده با تاموکسیفن
Background and Objective: Tamoxifen is the most commonly used treatment for the patients with breast cancer called ER +, which prevents the expression of genes that are effective in the growth and proliferation of cancer cells by estrogen. Resistant to Tamoxifen is a major clinical problem in breast cancer treatment. In recent studies, the role of microRNAs in tamoxifen resistance has been rais...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 2011 شماره
صفحات -
تاریخ انتشار 2011