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Published on: October 6, 2019
The interferon-alpha regulation of interferon regulatory factor 1 (IRF-1) and IRF-2 has therapeutic implications in
1Endocrine Oncology Unit of Internal Medicine, Uppsala University Hospital, Sweden.
Background:
Interferon regulatory factor 1 (IRF-1) has been demonstrated to possess antiproliferative and tumor suppressor functions, on the contrary. IRF-2 has been suggested to induce oncogenetic effect in some cell lines, but not evaluated in tumor patients.
Patients And Methods:
In 35 carcinoid tumor patients, expressions of IRF-1 and IRF-2 were investigated by immunohistochemistry and their values were analyzed with clinical treatment response. In carcinoid tumor cell line, Bonl, effects of IFN-alpha on the expression of both IRF-1 and IRF-2 mRNAs and proteins were determined by Northern blot, RNase protection assays and Western blot analysis.
Results:
IFN-alpha up-regulated the expression of IRF-1 and IRF-2 both in vivo and in vitro. In carcinoid tumors, IFN-alpha treatment led to a significant increase in the expression of IRF-1 (P < 0.001) and IRF-2 (P < 0.001). Moreover, the IRFs induction was correlated with the clinical response of IFN-alpha treatment, although their baseline values were not predictive. In addition, expressions of IRF-1 and IRF-2 were significantly correlated with the p68 kinase expression (P = 0.032 and P = 0.0176, respectively) and the expression of IRF-1 protein was positively correlated with that of IRF-2 (r = 0.671, P = 0.0001) tested in the same specimens.
Conclusions:
IRF-1 as well as IRF-2 have therapeutic implications in carcinoid tumors during treatment with interferon-alpha and IRFs induction might be used as indicators of response to treatment with interferon-alpha.
Insights
Interferon regulatory factors (IRFs) induction by interferon-alpha correlates with treatment response in carcinoid tumors. IRF-1 and IRF-2 show therapeutic potential and can indicate patient response to interferon-alpha therapy.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Interferon regulatory factor 1 (IRF-1) exhibits antiproliferative and tumor suppressor functions.
- Interferon regulatory factor 2 (IRF-2) is implicated in oncogenesis but its role in tumor patients is underexplored.
Purpose of the Study:
- To investigate the expression of IRF-1 and IRF-2 in carcinoid tumors.
- To analyze the correlation between IRF expression, interferon-alpha (IFN-alpha) treatment, and clinical response.
- To evaluate the effect of IFN-alpha on IRF-1 and IRF-2 expression in vitro and in vivo.
Main Methods:
- Immunohistochemistry was used to assess IRF-1 and IRF-2 expression in 35 carcinoid tumor patients.
- Northern blot, RNase protection assays, and Western blot analysis were employed to determine mRNA and protein expression in the Bonl carcinoid cell line.
- Expression levels were analyzed in relation to clinical treatment response.
Main Results:
- IFN-alpha significantly up-regulated IRF-1 and IRF-2 expression both in vivo and in vitro in carcinoid tumors (P < 0.001).
- IRF induction correlated with clinical response to IFN-alpha treatment, but baseline levels were not predictive.
- IRF-1 and IRF-2 expression correlated with p68 kinase expression and IRF-1 protein positively correlated with IRF-2 (r = 0.671, P = 0.0001).
Conclusions:
- IRF-1 and IRF-2 hold therapeutic implications for carcinoid tumors treated with interferon-alpha.
- The induction of IRFs can serve as potential biomarkers for predicting response to interferon-alpha therapy.
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