Insulin-like Growth Factor I (IGF-I) modulates hMOR transcription in neuronal cells: role of STAT3

IGF-I plays a pivotal role in neuronal cell survival, proliferation and diff erentiation through PI3K, MAPK/AP-1 and JAK/Stat3 activation. hMOR promoter has been shown to bear binding sites for both AP-1 and Stat1/3. MOR up-regulation contributes to neuronal cell survival as well. In this study, we investigated whether IGF-I up-regulates hMOR transcription and the potential role of Stat3 in this process. We employed diff erent hMOR reporter plasmids, bearing both Stat1/3 and AP-1 responsive elements (from -1672 to -10 bp) or only this latter (from -1556 to -40 bp), to transiently transfect SH-SY5Y neuroblastoma cells. We observed that IGF-I (10 nM; 24 h) signifi cantly up-regulated hMOR transcription only when Stat1/3 binding site was present in the gene reporter construct. To better assess the role of Stat3 in IGF-I-mediated induction of hMOR transcription, we down-regulated Stat3 expression in SH-SY5Y cells by a specifi c siRNA and then performed hMOR reporter plasmid assays: Stat3 down-regulation prevented IGFI-induced hMOR transcription. Further studies carried out with hMOR promoter constructs encompassing the start codon are in progress. Our results show that IGF-I may activate hMOR transcription in neuronal cells via Stat3.