The Expression And Significance Of EphA2, Ras And MAPK In Gastric Cancer

BACKGROUND:Gastric cancer is the fourth most common cancer and the second leading cause of cancer-related deaths in the world. Surgical resection, chemotherapy and radiotherapy are mainstay of treatment for patients with gastric cancer. However, the prognosis of advanced gastric cancer is poor with an estimated5-year survival rate of about25%worldwide. Post-surgical recurrence and metastasis are key factors for prognosis of patients with gastric cancer. It is imperative for us to further investigate the mechanisms of invasion and metastasis of gastric cancer.Epithelial-mesenchymal transition(EMT) play an important role in invasion and metastasis of carcinomas. Rat sarcoma-mitogen-activated protein kinase(Ras-MAPK) is a key signaling pathway of EMT. The mutation of K-Ras and high expression of Erkl/2positively correlates with the tumorigenesis and advancement of gastric cancer. Receptor tyrosine kinases(RTKs) induce EMT via activating its downstream signal molecules,such as Ras and MAPK. Erythropoietin-producing human hepatocellular(Eph) is the largest family member of RTKs. EphA2is one of Eph members,and its high expression is detected in gastric cancer. Inhibiting the expression of EphA2in gastric cancer induce the increasing expression of E-cadherin. This demonstrate that EphA2probable participate EMT of gastric cancer. However, whether EphA2enhance invasion and metastasis through Ras-MAPK signaling pathway participating EMT in gastric cancer is still unclear.OBJECTIVE:To investigate the relationship between EphA2and Ras-MAPK signaling pathway in gastric cancer.METHODS:1. The expression of EphA2, mutant K-Ras and Erkl/2in35specimens of gastric cancer tissues was detected by immunohistochemistry (IHC). The relationship among their expression was statistically analyzed.2. The expression levels of EphA2, mutant K-Ras and Erk1/2mRNA and proteins in gastric cancer cell lines AGS and SGC-7901was detected using real-time reverse transcription-polymerase chain rection (real-time RT-PCR) and western blot respectively. To investigate the different expression of EphA2, mutant K-Ras and Erk1/2in different differentiation of gastric cancer cell lines.RESULTS:1. Positive correlation between EphA2and mutant K-Ras, EphA2and Erk1/2, mutant K-Ras and Erk1/2was observed(P<0.05).2. The expression of EphA2, mutant K-Ras and Erk1/2in moderate grade differentiation gastric cancer cell line is significant higher than that of in low grade differentiation gastric cancer cell line(P<0.05).CONCLUSION:1. Positive correlation between EphA2and mutant K-Ras, EphA2and Erk1/2, mutant K-Ras and Erk1/2was observed.2. The expression levels of EphA2, mutant K-Ras and Erk1/2are probable correlate with the grade of differentiation of gastric cancer cells.