| 摘要: |
| 目的:检测胃癌中NR4A2(又称Nurr1)基因的表达,从NR4A2调控机制出发寻找相关选择性剪接异构体,探讨其与胃癌发生和转移的关系。方法:通过选择性剪接数据库(ASD)预测NR4A2基因可能存在的选择性剪接异构体,半定量PCR检测NR4A2及异构体的表达,基因测序技术鉴定新的剪接异构体；实时定量PCR检测41例样本中NR4A2及剪接异构体的表达水平；免疫组织化学方法检测28例样本中NR4A2蛋白表达。结果:NR4A2基因在胃癌原位、癌旁、转移组织中均有表达,确定了2种剪接异构体NR4A2-Ⅰ和NR4A2-Ⅱ。实时定量PCR检测41例样本中NR4A2及2种异构体在癌旁组织表达水平高于原位癌 (P= 0.017,P=0.007,P=0.004)；在肝转移灶中表达水平低于原位癌(P=0.001,P=0.018,P=0.016),差异有统计学意义。免疫组化检测发现癌旁组织中NR4A2表达阳性率高于原位癌及转移灶,但差异无统计学意义(P=0.672)。结论:胃癌原位、癌旁和转移组织中至少存在NR4A2基因的2种剪接模式；NR4A2及异构体的表达变化与胃癌发生和转移相关。 |
| 关键词: NR4A2 Nurr1 胃肿瘤 剪接异构体 |
| DOI：10.3724/SP.J.1008.2009.01004 |
| 投稿时间：2009-02-19修订日期：2009-07-30 |
| 基金项目: |
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| NR4A2 and its splicing variants contribute to tumorigenesis and metastasis of gastric cancer |
| LIU Xiao-kang1,LIN Li-ping2,CHANG Wen-jun2,GU Li-qiang1,CAO Guang-wen2*,MA Li-ye1* |
| (1.Department of General Surgery,Changhai Hospital,Second Military Medical University,Shanghai 200433,China;2.Department of Epidemiology,College of Basic Medical Sciences,Second Military Medical University,Shanghai 200433) |
| Abstract: |
| Objective:To investigate the expression of NR4A2(Nurr1) and its splicing variants in gastric cancer,and to evaluate their potential association with the pathogenesis and metastasis of gastric carcinoma.Methods: Alternative Splicing Database (ASD) was used to predict the possible splicing variants of NR4A2; they were identified by gene sequencing technique and their expression was detected by semi-quantitative PCR.The mRNA expression of NR4A2 and its splicing variants in tumor and the corresponding adjacent-tumor tissues (n=41) were determined by real-time PCR.Meanwhile,immunohistochemisty was employed to examine the protein levels of NR4A2 in the tumor tissues (n=28).Results: The expression of NR4A2 mRNA was observed in the primary tumor tissues,adjacent tumor tissues, and metastatic tissues.Two splicing variants of NR4A2 were discovered:NR4A2-Ⅰ and NR4A2-Ⅱ.The mRNA expression of NR4A2, NR4A2-Ⅰ,and NR4A2-Ⅱ in the adjacent-tumor tissue was significantly higher than that in the primary tumor tissue (P=0.017,P=0.007,and P=0.004),and that in the hepatic metastatic tissue was significantly lower than that in the primary tumor tissue (P=0.001,P=0.018,P=0.016).Meanwhile,immunohistochemistry showed that the positive rate of NR4A2 protein was higher in adjacent-tumor tissue than that in both tumor tissues and metastatic tissues,but with no significant differences.Conclusion: At least there are 2 splicing variants of NR4A2 in the gastric tumor,adjacent-tumor,and metastatic tissues; NR4A2 and the novel splicing variants may contribute to the pathogenesis and metastasis of gastric malignancy. |
| Key words: NR4A2 Nurr1 gastric carcinoma alternative splicing |
