Abstract

There is evidence that platelet-derived growth factor (PDGF) is involved in the development of numerous human tumor types. The evidence is most complete in thecase of glioblastomas cells. Although many signal transduction pathways have several steps shared with PDGF, we found that inhibition of Jun kinase N-terminalkinase ( JNK) stimulate gliomas in an autocrine fashion. Here, we have investigated the role of PDGF in the regulation of human T98G glioblastoma cells grown,in both the presence and absence of a small interfering RNA (siRNA) against Jun-N-Terminal Kinase one ( JNK1). Treatment of T98G cells with PDGF alonemultiplied substantially faster than untreated cells. In contrast, cells treated with siRNA against JNK-1 led to a reduction in growth rate and DNA synthesis, whilecells treated with a combination of PDGF and siRNA failed to alter the growth rate, DNA synthesis and cell proliferation as compared to cells treated only witheither, PDGF or siRNA against JNK1 alone. The inhibition of JNK-1 expression by siRNA leads to a marginal inhibition of NF-κB transcriptional activity andstrongly reduced the transcriptional activity of the activator protein-1 (AP-1) in presence of PDGF. The reduction was more evident in presence of PMA, a positivecontrol which usually increase the activity of JNK-1 kinase. In conclusion, our results suggest that siRNA against c-Jun N terminal kinase 1 might have an importantrole in regulating the expression and effect of PDGF in glioblastoma cells.