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

Citation
Y. Zhou et al., The interferon-alpha regulation of interferon regulatory factor 1 (IRF-1) and IRF-2 has therapeutic implications in carcinoid tumors, ANN ONCOL, 11(6), 2000, pp. 707-714
Citations number
29
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
ANNALS OF ONCOLOGY
ISSN journal
09237534 → ACNP
Volume
11
Issue
6
Year of publication
2000
Pages
707 - 714
Database
ISI
SICI code
0923-7534(200006)11:6<707:TIROIR>2.0.ZU;2-X
Abstract
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 a nalyzed with clinical treatment response. In carcinoid tumor cell line, Bon 1, 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 Wes tern blot analysis. Results: IFN-alpha up-regulated the expression of IRF-1 and IRF-2 both in v ivo and in vitro. In carcinoid tumors, IFN-alpha treatment led to a signifi cant 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 wit h the p68 kinase expression (P = 0.032 and P = 0.0176, respectively) and th e 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 carcin oid tumors during treatment with interferon-alpha and IRFs induction might be used as indicators of response to treatment with interferon-alpha.