NR4A2 and its splicing variants contribute to tumorigenesis and metastasis of gastric cancer
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    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.

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History
  • Received:February 19,2009
  • Revised:July 30,2009
  • Adopted:August 25,2009
  • Online: September 17,2009
  • Published:
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