The interferon-alpha 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 beendemonstrated to possess antiproliferative and tumor suppressor functions, onthe contrary, IRF-2 has been suggested to induce oncogenetic effect in somecell lines, but not evaluated in tumor patients.Patients and methods:In 35 carcinoid tumor patients, expressionsof IRF-1 and IRF-2 were investigated by immunohistochemistry and their valueswere analyzed with clinical treatment response. In carcinoid tumor cell line,Bon1, effects of IFN- on the expression of both IRF-1 and IRF-2 mRNAs andproteins were determined by Northern blot, RNase protection assays and Westernblot analysis.Results:IFN- up-regulated the expression of IRF-1 and IRF-2both in vivoand in vitro. In carcinoid tumors, IFN-treatment led to a significant increase in the expression of IRF-1 (P< 0.001) and IRF-2 (P < 0.001). Moreover, the IRFs inductionwas correlated with the clinical response of IFN- treatment, althoughtheir baseline values were not predictive. In addition, expressions of IRF-1and IRF-2 were significantly correlated with the p68kinaseexpression (P = 0.032 and P = 0.0176, respectively) and theexpression 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 implicationsin carcinoid tumors during treatment with interferon- and IRFs inductionmight be used as indicators of response to treatment with interferon-.