title: WAP four-disulfide core domain protein 2 mediates the proliferation             of human ovarian cancer cells through the regulation of growth- and apoptosis-associated             genes.
abstract: The WAP four-disulfide core domain protein 2 (WFDC2) is frequently overexpressed             in epithelial ovarian cancer cells and has been proposed as a potential biomarker.             The biological function of WFDC2 in tumor progression remains unclear. In this             study, the stable expression of short hairpin RNA (shRNA) against WFDC2 in the             human ovarian SKOV3 cell line was established. Cell proliferation in vitro was             determined by MTT assay. Cell cycle and apoptosis were analyzed by FACS. The expression             of genes related to cell proliferation and survival was detected by real-time             RT-PCR and western blotting. In vivo tumor growth assay was performed by establishing             WFDC2-knockdown xenografts in nude mice and monitoring tumor growth. The expression             of WFDC2, Ki67 and activated caspase-3 was analyzed by immunohistochemistry in             order to determine the role of WFDC2 in proliferation and apoptosis. Our results             revealed that the silencing of WFDC2 abolished ovarian cancer cell proliferation,             suppressing tumor formation and growth in ovarian cancer cells both in vitro and             in vivo. The knockdown of WFDC2 induced upregulation of Fasl and the downregulation             of cyclin D1 activated caspase-3 and Ki67. These results indicate that WFDC2 plays             a crucial role in tumor formation and growth in ovarian cancer cells. WFDC2 may             be a potential therapeutic target for epithelial ovarian cancer.
authors.affiliation: School of Biotechnology, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.forename: Xia
authors.initials: X
authors.lastname: Mu
authors.forename: Suihai
authors.initials: S
authors.lastname: Wang
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.forename: Yingsong
authors.initials: Y
authors.lastname: Wu
authors.forename: Jiliang
authors.initials: J
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: C530104:CCND1 protein, human; D053222:Fas Ligand Protein; D019394:Ki-67 Antigen; D011506:Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human; D019938:Cyclin D1; D053148:Caspase 3