Significant biological role of sp1 transactivation in multiple myeloma

Clin Cancer Res. 2011 Oct 15;17(20):6500-9. doi: 10.1158/1078-0432.CCR-11-1036. Epub 2011 Aug 19.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Bone Marrow Cells
  • Cell Cycle / genetics*
  • Cell Proliferation
  • Cell Survival / genetics*
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Masoprocol / analogs & derivatives
  • Masoprocol / pharmacology
  • Melanoma, Experimental / genetics
  • Mice
  • Mice, SCID
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / metabolism
  • RNA Interference
  • Sp1 Transcription Factor / genetics*
  • Sp1 Transcription Factor / metabolism
  • Transcriptional Activation*
  • Tumor Cells, Cultured


  • Sp1 Transcription Factor
  • terameprocol
  • Masoprocol