Hif2 Alpha Is Associated With Poor Prognosis And Affects The Expression Levels Of Survivin And Cyclin D1 In Gastric Carcinoma

Hypoxia-inducible factor-2 alpha (HIF2 alpha) is a major determinant factor of invasion and metastasis in various tumors. It has been reported that HIF2 alpha is overexpressed in many tumors, including gastric cancer. However, the roles of HIF2 alpha in the progression of gastric cancer are still not clear. In this study, we first examined the levels of HIF2 alpha in gastric cancer by using immunohistochemistry, western blot and real-time PCR analysis. The results showed that HIF2 alpha was highly expressed in gastric cancers compared to non-neoplastic mucosa and significantly correlated with histologic grade, TNM stages and peritoneal dissemination. MTT and colony formation assay revealed HIF2 alpha overexpression induced high proliferation in BGC823 cells and HIF2 alpha knockdown significantly inhibited proliferation in SGC7901 cells. Furthermore, we demonstrated that HIF2 alpha could promote migration and invasion in gastric cancer cells. The results of western blot and RT-PCR analysis indicated that Survivin, Cyclin D1, MMP2 and MMP9 are upregulated with HIF2 alpha overexpression. Finally, similar roles of HIF2 alpha also in vivo were demonstrated. Taken together, the present study suggested that HIF-2 alpha was involved in proliferation, metastasis and invasion of gastric cancer cells, with the induction of Survivin, Cyclin D1, MMP2 and MMP9 expression.