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
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.