title: Significant biological role of sp1 transactivation in multiple myeloma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Fulciniti
authors.forename: Samir
authors.initials: S
authors.lastname: Amin
authors.forename: Puru
authors.initials: P
authors.lastname: Nanjappa
authors.forename: Scott
authors.initials: S
authors.lastname: Rodig
authors.forename: Rao
authors.initials: R
authors.lastname: Prabhala
authors.forename: Cheng
authors.initials: C
authors.lastname: Li
authors.forename: Stephane
authors.initials: S
authors.lastname: Minvielle
authors.forename: Yu-Tzu
authors.initials: YT
authors.lastname: Tai
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Tassone
authors.forename: Herve
authors.initials: H
authors.lastname: Avet-Loiseau
authors.forename: Teru
authors.initials: T
authors.lastname: Hideshima
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.forename: Nikhil C
authors.initials: NC
authors.lastname: Munshi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001854:Bone Marrow Cells; D002453:Cell Cycle / Q000235:genetics*; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D009637:Masoprocol / Q000031:analogs & derivatives / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000235:genetics; D051379:Mice; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D016329:Sp1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
chemical_list: D016329:Sp1 Transcription Factor; C076852:terameprocol; D009637:Masoprocol