摘要
目的:研究SYT-SSX融合基因不同亚型在滑膜肉瘤中的表达情况,从蛋白质水平研究不同融合基因类型在细胞周期因子cyclinD1、cDK4、p21WAF1/CIP1、p27等表达上的差异,从而为进一步探索融合基因的作用机制提供实验依据。方法:选取天津医科大学附属肿瘤医院1974年4月~2005年8月收治的滑膜肉瘤患者中SYT-SSX融合基因表达阳性的病例54例,提取石蜡包埋组织中的RNA,通过逆转录-聚合酶链反应检测SYT-SSX亚型的表达,制作组织芯片,使用免疫组织化学染色的方法检测不同类型融合基因CvclinD1、CDK4、p21WAF1/CIP1、p27的表达情况,比较这些细胞周期相关蛋白分别在SYT-SSX1和SYT-SSX2阳性病例中的表达差异。结果:54例滑膜肉瘤患者中SYT-SSX1型患者22例(40.74%),SYT-SSX2型患者32例(59.26%),SYT-SSX1与SYT-SSX2阳性滑膜肉瘤中,CyclinD1,CDK4,p21WAF1/CIP1和p27表达差异有统计学意义(P<0.05)。结论:SSX1型滑膜肉瘤患者与SYT-SSX2型患者相比,肿瘤具有更强的增殖能力;SSX1型的融合基因表达更多的CyclinD1/CDK4,而表达较少的抑制肿瘤的CDI家族p21 WAF1/CIP1、p27,提示可能是因为SSX1促发了某种转录机制使得细胞较SSX2型更易进入细胞周期而获得恶性表型,同时促使肿瘤细胞逃避细胞增殖的监督机制。
Objective: The aim of this research was to study the classification of SYT-SSX fusion genes in synovial sarcoma (SS) and to investigate the function of these fusion genes in the cell cycle. Hopefully these results will elicit a novel path to discover the function of the fusion genes in SS. Methods: RNA was extracted from 54 paraffin embedded SS tissues known to express SYT-SSX fusion genes. RT-PCR was used to classify the type of fusion gene in each tissue as either SYT-SSXl or SYT-SSX2. The typical parameters were used to manufacture the tissue microarray. The expression level of CyclinD1, CDK4, p21WAF1/CIP1 and p27 were examined by immunohistochemistry. Labeling index was used to evaluate the entire staining status of each slide. Results: Of the 54 patient tissues, there were 22 (40.74%) cases with type SYT-SSX1 fusion gene and 32 (59.26%) cases with type SYT-SSX2 fusion gene. Significant differences in the expression levels of CyclinD1, CDK4, p21WAF1/CIP1 and p27 were seen between the different types of fusion genes (P〈0.05). Conclusion: The proliferation index of SSXl is higher than that of SSX2. The fusion gene of SYT-SSXl could increase the expression of CyclinD1/CDK4 genes and decrease the expression of p21WAF1/CIP1 and p27 genes. We hypothesize that SYT-SSXl and SYT-SSX2 may differ in transcriptional deregulation of one or more key genes involved in the regulation of mesenchymal cells to switch on the cell cycle and escape the mechanism of supervision.
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2010年第10期566-569,共4页
Chinese Journal of Clinical Oncology
基金
国家自然科学基金资助(编号:30572097)~~