Annals of Oncology 11:707-714, 2000
© 2000 European Society for Medical Oncology
research-article |
The interferon-
regulation of interferon regulatory factor 1 (IRF-1) and IRF-2 has therapeutic implications in carcinoid tumors
Endocrine Oncology Unit of Internal Medicine. Uppsala University Hospital Uppsala, Sweden
Correspondence to: Prof. K. Öberg, Endocrine Oncology Unit of Internal Medicine, Uppsala University Hospital, S751 85, Uppsala, Sweden. E-mail: Kjell.Oberg{at}medicin.uu.se
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 immuno-histochemistry and their values were analyzed with clinical treatment response. In carcinoid tumor cell line, Bonl, effects of IFN-
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- up-regulated the expression of IRF-1 and IRF-2 both in vivo and 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 induction was correlated with the clinical response of IFN- 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 inter-feron- and IRFs induction might be used as indicators of response to treatment with interferon-
gene expression, IRF-1 and IRF-2, p68, PKR, signal transduction
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