Activation of Stat3 and Stat1 DNA binding and transcriptional activity in human brain tumour cell lines by gp130 cytokines

In this study we examine the activation of the latent Stat family of transc ription factors by the gp130 family of cytokines in cell lines derived from human brain tumours. Of the cytokines tested, oncostatin M resulted in the most dramatic induction of Stat1 and Stat3 in all cell lines analysed, as assessed by the formation of protein/DNA complexes. Interleukin-6, leukemia inhibitory factor, and ciliary neurotrophic factor also induced Stat compl exes more selectively and to a lesser magnitude than oncostatin M. The kine tics of Stat1 and Stat3 activation was rapid and transient; the nuclear acc umulation of DNA binding-proficient Stat protein was detected in the nucleu s within minutes of cytokine induction. The transcriptional potential of th e oncostatin M-activated Stat molecules was demonstrated in two glioma cell lines (U87-MG, SNB-19) by transient transfection experiments using a Stat- responsive reporter plasmid. Oncostatin M-dependent transcription from this reporter plasmid was reduced to uninduced levels by the inclusion of a dom inant-negative Stat3 molecule, demonstrating that Stat molecules were respo nsible for the induction. These studies demonstrate that oncostatin M is th e most potent activator of Stat molecules in a variety of brain tumour-deri ved cell lines, an observation that could have implications affecting the b alance between proliferation/apoptosis of these cells. (C) 2000 Elsevier Sc ience Inc. All rights reserved.