Abstract LB-286: 3p24 tumor suppressor gene RBMS3 in NPC

Abstract

Abstract Deletion within the 3p chromosomal region are one of the most frequent genetic alterations in many solid tumors, including nasopharyngeal carcinoma (NPC), suggesting the existence of one or more tumor suppressor genes (TSGs) within the frequently deleted region. A putative TSG RBMS3, located at the frequently deleted region 3p24-p23, has been identified in our previous study. Here, we reported that down-regulation of RBMS3 was detected in 3/3 (100%) NPC cell lines and 13/15 (86.7%) primary NPC tissues. Functional analysis demonstrated that RBMS3 was able to suppress tumorigenicity of NPC cells both in vitro and in vivo, including inhibiting the cell growth rate, colony formation in vitro and tumor formation in nude mice. Additionally, the tumor suppressive mechanism of RBMS3 was associated with its role in cell cycle arrest at the G1/S checkpoint by the up-regulation of p53, and p21, the down-regulation of Smad4, cyclin D1, cyclin E/CDK2, and the subsequent inhibition of Rb-ser780. Further analysis demonstrated that RBMS3 had a pro-apoptotic role in a mitochondrial-dependent manner via activation of caspase-9 and PARP. Finally, RBMS3 inhibited microvessel formation, which may be mediated by down-regulation of β-catenin and inactivation of its downstream targets, including c-Myc, MMP7, MMP9, and MMP2. Taken together, our findings define a function for RBMS3 as an important tumor suppressor gene in NPC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-286. doi:1538-7445.AM2012-LB-286