Institute of Pharmacology, National Yang-Ming University, Taiwan, ROC.
Cancer Lett. 2010 Feb 1;288(1):75-85. doi: 10.1016/j.canlet.2009.06.025. Epub 2009 Jul 30.
Members of the suppressor of cytokine-induced signaling (SOCS) family are negative regulators of cytokine signaling pathways. By mRNA differential display, we showed that SOCS6 was frequently down-regulated in gastric cancer (GC). Our data showed that allelic loss and promoter hypermethylation may account for the major mechanisms leading to SOCS6 inactivation. Ectopic expression of SOCS6 suppressed cell growth and colony formation, in part through eliciting intrinsic apoptotic pathway, accompanied with decreased mitochondrial membrane potential. Taken together, this study provides molecular and functional data supporting the importance of loss-of-function of SOCS6 as a frequent event in gastric tumorigenesis.
抑制细胞因子信号转导(SOCS)家族的成员是细胞因子信号通路的负调节剂。通过 mRNA 差异显示,我们发现 SOCS6 在胃癌(GC)中经常下调。我们的数据表明,等位基因缺失和启动子超甲基化可能是导致 SOCS6 失活的主要机制。SOCS6 的异位表达抑制了细胞生长和集落形成,部分原因是通过引发内在凋亡途径,伴随着线粒体膜电位降低。综上所述,这项研究提供了分子和功能数据,支持 SOCS6 功能丧失作为胃癌发生的常见事件的重要性。