Tumor suppressor MDA-7/IL-24 selectively inhibits vascular smooth muscle cell growth and migration

Jiyuan Chen, Sunil Chada, Abner Mhashilkar, Joseph M. Miano

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Abnormalities in smooth muscle cell (SMC) proliferation and differentiation underlie the pathogenesis of proliferative vascular diseases. MDA-7 (HUGO approved symbol IL24) is a unique gene, originally identified as a tumor suppressor and more recently shown to have cytokine activity. MDA-7/IL24 has been implicated in apoptosis and cellular differentiation in tumor cells and in tumor invasion/metastasis in clinical specimens - properties central to SMC remodeling during proliferative vascular diseases. In this study, we evaluated the effects of overexpressing MDA-7/ IL24 in various SMC: the apparently "normal" rat PAC1 cell line, primary human coronary artery SMC, and normal rat aortic SMC. We transduced SMC with adenovirus-mda7 (Ad-mda7) or control virus (Ad-Luc) and assessed cell viability, apoptosis, and migration. Ad-mda7 suppressed PAC1 cell growth in a dose-dependent manner while having no effect on normal primary human coronary artery cells or rat aortic SMC, despite strong expression of the MDA-7 transgene in all SMC. Similarly, Ad-mda7 treatment induced apoptosis in PAC1 cells with essentially no effect on normal coronary and rat aortic SMC. Ad-mda7 also inhibited serum-stimulated PAC1 cell migration. Karyotype analysis of PAC1 cells revealed that they exhibit multiple chromosomal aberrations. Importantly, recombinant MDA-7 did not elicit cell death or STAT-3 activation in PAC1 SMC, suggesting that the effects of Ad-mda7 were mediated through an intracellular pathway. These data demonstrate that Ad-mda7 exhibits selectivity in apoptosis induction and growth suppression in an atypical SMC line, raising new questions pertaining to heterogeneity in SMC death susceptibility.

Original languageEnglish (US)
Pages (from-to)220-229
Number of pages10
JournalMolecular Therapy
Volume8
Issue number2
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

Keywords

  • Adenoviral vector
  • Apoptosis
  • Heterogeneity
  • Interleukin-24
  • MDA-7
  • Migration
  • Proliferation
  • Smooth muscle cell

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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