Significant Biological Role of Sp1 Transactivation in Multiple Myeloma

Overview

Journal Clin Cancer Res

Specialty Oncology

Date 2011 Aug 23

PMID 21856768

Citations 34

Authors

Mariateresa Fulciniti

Samir Amin

Puru Nanjappa

Scott Rodig

Rao Prabhala

Cheng Li

Stephane Minvielle

Yu-Tzu Tai

Pierfrancesco Tassone

Herve Avet-Loiseau

Teru Hideshima

Kenneth C Anderson

Nikhil C Munshi

Affiliations

Soon will be listed here.

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.

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