title: HIF2α is associated with poor prognosis and affects the expression levels of survivin and cyclin D1 in gastric carcinoma.
abstract: Hypoxia-inducible factor-2α (HIF2α) is a major determinant factor of invasion and metastasis in various tumors. It has been reported that HIF2α is overexpressed in many tumors, including gastric cancer. However, the roles of HIF2α in the progression of gastric cancer are still not clear. In this study, we first examined the levels of HIF2α in gastric cancer by using immunohistochemistry, western blot and real-time PCR analysis. The results showed that HIF2α 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 HIF2α overexpression induced high proliferation in BGC823 cells and HIF2α knockdown significantly inhibited proliferation in SGC7901 cells. Furthermore, we demonstrated that HIF2α 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 HIF2α overexpression. Finally, similar roles of HIF2α also in vivo were demonstrated. Taken together, the present study suggested that HIF-2α was involved in proliferation, metastasis and invasion of gastric cancer cells, with the induction of Survivin, Cyclin D1, MMP2 and MMP9 expression.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang 110001, P.R. China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Tong
authors.affiliation: Department of Laboratory Medicine, ShengJing Affiliated Hospital, China Medical University, Shenyang 110001, P.R. China.
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Tong
authors.affiliation: Department of Endocrinology and Metabolism, The First Affiliated Hospital, China Medical University, Shenyang 110001, P.R. China.
authors.forename: Xie-Xiao
authors.initials: XX
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang 110001, P.R. China.
authors.forename: Hua-Chuan
authors.initials: HC
authors.lastname: Zheng
authors.affiliation: The 31st Middle School, Shenyang 110000, P.R. China.
authors.forename: Yin-Zhao
authors.initials: YZ
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*; D000077022:Survivin; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D019938:Cyclin D1; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D000099162:Endothelial PAS Domain-Containing Protein 1; C107489:BIRC5 protein, human; C530104:CCND1 protein, human