The interferon-α regulation of interferon regulatory factor 1 (IRF-1) and IRF-2 has therapeutic implications in carcinoid tumors

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, Bon1, 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.