Data from Downregulation of RBMS3 Is Associated with Poor Prognosis in Esophageal Squamous Cell Carcinoma

Abstract

<div>Abstract<p>Deletions on chromosome 3p occur often in many solid tumors, including esophageal squamous cell carcinoma (ESCC), suggesting the existence at this location of one or more tumor suppressor genes (TSG). In this study, we characterized <i>RBMS3</i> gene encoding an RNA-binding protein as a candidate TSG located at 3p24. Downregulation of <i>RBMS3</i> mRNA and protein levels was documented in approximately 50% of the primary ESCCs examined. Clinical association studies determined that <i>RBMS3</i> downregulation was associated with poor clinical outcomes. <i>RBMS3</i> expression effectively suppressed the tumorigenicity of ESCC cells <i>in vitro</i> and <i>in vivo</i>, including by inhibition of cell growth rate, foci formation, soft agar colony formation, and tumor formation in nude mice. Molecular analyses revealed that <i>RBMS3</i> downregulated c-Myc and CDK4, leading to subsequent inhibition of Rb phosphorylation. Together, our findings suggest a tumor suppression function for the human <i>RBMS3</i> gene in ESCC, acting through c-Myc downregulation, with genetic loss of this gene in ESCC contributing to poor outcomes in this deadly disease. <i>Cancer Res; 71(19); 6106–15. ©2011 AACR</i>.</p></div>