State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
Cancer Res. 2011 Oct 1;71(19):6106-15. doi: 10.1158/0008-5472.CAN-10-4291. Epub 2011 Aug 15.
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 RBMS3 gene encoding an RNA-binding protein as a candidate TSG located at 3p24. Downregulation of RBMS3 mRNA and protein levels was documented in approximately 50% of the primary ESCCs examined. Clinical association studies determined that RBMS3 downregulation was associated with poor clinical outcomes. RBMS3 expression effectively suppressed the tumorigenicity of ESCC cells in vitro and in vivo, including by inhibition of cell growth rate, foci formation, soft agar colony formation, and tumor formation in nude mice. Molecular analyses revealed that RBMS3 downregulated c-Myc and CDK4, leading to subsequent inhibition of Rb phosphorylation. Together, our findings suggest a tumor suppression function for the human RBMS3 gene in ESCC, acting through c-Myc downregulation, with genetic loss of this gene in ESCC contributing to poor outcomes in this deadly disease.
3p 染色体缺失经常发生在许多实体瘤中，包括食管鳞状细胞癌 (ESCC)，提示在该位置存在一个或多个肿瘤抑制基因 (TSG)。在这项研究中，我们将编码 RNA 结合蛋白的 RBMS3 基因鉴定为位于 3p24 的候选 TSG。大约 50%的原发性 ESCC 中观察到 RBMS3 mRNA 和蛋白水平下调。临床关联研究确定 RBMS3 下调与不良临床结局相关。RBMS3 表达有效地抑制了 ESCC 细胞在体外和体内的致瘤性，包括抑制细胞生长速度、焦点形成、软琼脂集落形成以及裸鼠肿瘤形成。分子分析表明，RBMS3 下调了 c-Myc 和 CDK4，从而随后抑制了 Rb 的磷酸化。综上所述，我们的研究结果表明，人类 RBMS3 基因在 ESCC 中具有肿瘤抑制功能，通过下调 c-Myc 起作用，ESCC 中该基因的遗传缺失导致这种致命疾病的不良结局。
