The Effect Of Over-expression Her-2 On The Ivvasion/migration In Human Gastric Cancer Cell

Gastric cancer (GC) is the fourth most common cancer globally, and was the second most common cause of death due to malignancies worldwide in 2008. Multiple environmental factors including chronic Helicobacter pylori(H. pylori) infection, hereditary factors and dietary factors have been implicated in the initiation of gastric carcinogenesis. Although the understanding of neoplastic progression has improved in the past decade, the prognosisof patients with advanced GC remains relatively poor.Consequently, it is important to uncover the biological mechanisms underlying progression of the disease anddevelop strategies to intervene in this process.HER2 is a member of the epidermal growth factor receptor (EGFR) family and consists of an extracellular domain and an intracellular domain. HER2 can activate its downstream signal by dimerization, both as a homodimer and a heterodimer with other EGFR family receptors.HER2 overexpression is observed in 7-34% of GC cases and is correlated with clinicopathological features,including depth of tumor invasion, lymph node metastasis, intestinal-like subtype and tumor stage. In the ToGA study, standard chemotherapy regimens (capecitabine plus cisplatin or fluorouracil plus cisplatin)with trastuzumab resulted in longer survival times than those without trastuzumab in patients with HER2-positive GC. Median overall survival periods were 13.8 months in patients assigned to a trastuzumab plus chemotherapy group and 11.1 months in patients assigned to a chemotherapy alone group。As a central molecule in the Wnt signaling pathway, β-catenin expression is localized in the membrane, cytoplasm and nucleus.β-catenin has a dual role depending on its intracellular localization.Membranous expression of β-catenin is linked to E-cadherin and the actin cytoskeleton, and is responsible for cell-to-cell adhesion and exerting a restrictive effect on tumor growth. Cytoplasmic and nuclear P-catenin are mainly involved in regulation of the Wnt signaling pathway. It’s abnormal expression is closely related to the occurrence and development of tumor.Objective:To investigate the effect of Her-2 on invasion and metastasis of gastric cancer cell.To explore the relationship between Her-2 and P-catenin.Methods:l.Culturing gastric cancer cell lines BGC823.2.Perbb2-EGFP and p-EGFP were transfected into BGC823 cells through lipofectamine.The p-EGFP group was the negative control and the blank group was the blank control.3.Realtime PCR was employed to identify the mRNA expression of Her-2 in three groups of gastric cancer cells.4.Western blotting was employed to identify the protein expression of Her-2 and β-catenin in three groups of gastric cancer cells.5.Transwell model was employed to observe the invasion and migration of three groups of gastric cancer cells.Results:1.Compared witll p-EGFP group and blank group BGC823 cells,the mRNA expression of Her-2 was increased in Perbb2-EGFP group BGC823 cells (p<0.05).2.Compared witll p-EGFP group and blank group BGC823 cells,the protein expression of Her-2 and P-catenin was increased in Perbb2-EGFP group BGC823 cells (p<0.05).3.Compared witll p-EGFP group and blank group BGC823 cells,the invasion and migration ability had improved significantly in Perbb2-EGFP group BGC823 cells (p<0.05).Conclusion:1.The expression of Her-2 increased when gastric cancer cells was infected with Her-2 gene plasmid.2.Her-2 can enhance the ability of migration and invasion of gastric cancer cells.3.Her-2 could up-regulate the β-catenin expression,which indicated that β-catenin was relationship with the invasion and migration of gastric cancer cells.