NR4A2 and its splicing variants contribute to tumorigenesis and metastasis of gastric cancer
10.3724/SP.J.1008.2009.01004
- Author:
Xiao-Kang LIU
1
Author Information
1. Department of General Surgery
- Publication Type:Journal Article
- Keywords:
Alternative splicing;
Gastric carcinoma;
NR4A2;
Nurr1
- From:
Academic Journal of Second Military Medical University
2010;30(9):1004-1008
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the expression of NR4A2(Nurrl) 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.