Interferon alpha induction of Stat1 and Stat2 and their prognostic significance in carcinoid tumors

IFN-alpha has been shown to elicit antitumor activity in carcinoid tumors. In the present study the effects of IFN-alpha on the protein expression inv olved in the IFN-alpha signaling, which were recognized as signal transduce r and activators of transcription (Stats), were investigated. Archive speci mens from 45 carcinoid patients, 33 before IFN-alpha and 45 during treatmen t, were studied. The tissues were immunostained for protein expression by u sing monoclonal anti-Stat1 and anti-Stat2 antibodies. Results showed that S tat1 and Stat2 immunostaining were significantly increased during IFN-alpha treatment. Stats scores were significantly increased only in patients with objective response as well as those with stable disease but not in those w ith progressive disease. The induction of Stats correlated with the surviva l rates of the patients. In addition, both Stat scores significantly correl ated with the p68 protein expression. In a carcinoid tumor cell line, Bon1, IFN-alpha dose-dependently increased the Stat expression. Analysis of cell fractions showed that IFN-alpha increased Stat protein both in cytoplasm a nd nucleoplasm of the cells. Furthermore, IFN-alpha enhanced tyrosine phosp horylation of Stat1 and Stat2. Thus, the antitumor effect, in vivo and in v itro, in IFN-alpha -treated carcinoid tumors seems to be mediated via upreg ulation of Stat proteins and enhancement of phosphorylation of these protei ns. Copyright (C) 2001 S. Karger AG, Basel.