Signal Transducer and Activator of Transcription 1 (Stat1) Maintains Basal mRNA Expression of Pro-Survival Stat3-Target Genes in Glioma C6 Cells

The STAT family of transcription factors has 6 members, participating in signal transduction from cytokine and growth factor receptors to the cell nucleus. In many cancers STAT3 plays a key role in transducing the signals stimulating proliferation and viability, whereas STAT1 participates in the inflammatory response, with potential anti-tumour effects. Possibility of selectively inhibiting STAT3 activity is intensely studied, as a possible anti-cancer strategy. However, the role of a particular STAT may differ in different cancers, in particular gliomas. In our work, we studied the effects of STAT1 and STAT3 on expression of STAT3-target genes: Bcl2l1, Ccnd1 and Myc, as well as a STAT-driven reporter construct, in the rat C6 glioma. We employed DNA decoys and siRNAs against either STAT, as well as overexpression of either STAT protein. Our results demonstrate that in the C6 glioma cells it is Stat1, and not Stat3, that maintains the basal expression of Bcl2l1 and possibly Myc, and that both STATs bind to the Myc promoter. In agreement with these results, the overexpression of STAT1 stimulated, whereas of STAT3 inhibited the expression of the STAT-driven reporter construct. Our results point to a potential oncogenic role of STAT1 in the C6 glioma cells.

17 April 2012