ARTICLE ABSTRACT
Purpose: The transcription factor specificity protein 1 (Sp1) controls number of cellular processes by regulating the expression of critical cell cycle, differentiation, and apoptosis-related genes containing proximal GC/GT-rich promoter elements. We here provide experimental and clinical evidence that Sp1 plays an important regulatory role in multiple myeloma (MM) cell growth and survival.Experimental Design: We have investigated the functional Sp1 activity in MM cells using a plasmid with Firefly luciferase reporter gene driven by Sp1-responsive promoter. We have also used both siRNA- and short hairpin RNA–mediated Sp1 knockdown to investigate the growth and survival effects of Sp1 on MM cells and further investigated the anti-MM activity of terameprocol (TMP), a small molecule that specifically competes with Sp1-DNA binding in vitro and in vivo.Results: We have confirmed high Sp1 activity in MM cells that is further induced by adhesion to bone marrow stromal cells (BMSC). Sp1 knockdown decreases MM cell proliferation and induces apoptosis. Sp1-DNA binding inhibition by TMP inhibits MM cell growth both in vitro and in vivo, inducing caspase-9–dependent apoptosis and overcoming the protective effects of BMSCs.Conclusions: Our results show Sp1 as an important transcription factor in myeloma that can be therapeutically targeted for clinical application by TMP. Clin Cancer Res; 17(20); 6500–9. ©2011 AACR.
