title: OVA66, a tumor associated protein, induces oncogenic transformation of NIH3T3 cells.
abstract: The tumor associated antigen OVA66 has been demonstrated to be highly expressed in malignant tumors and implicated in various cellular processes. To further elucidate its oncogenic character, we established an OVA66 stably overexpressed NIH3T3 cell line and a vector transfected control, named NIH3T3-flagOVA66 and NIH3T3-mock, respectively. NIH3T3-flagOVA66 cells showed faster cell cycling, proliferation, cell migration and more resistance to 5-fluorouracil-induced apoptosis. When NIH3T3-flagOVA66 and NIH3T3-mock cells were injected into nude mice for xenograft tumorigenicity assays, the NIH3T3-flagOVA66 cells formed tumors whereas no tumors were observed in mice inoculated with NIH3T3-mock cells. Analysis of PI3K/AKT and ERK1/2 MAPK signaling pathways by serum stimulation indicated hyperactivation of AKT and ERK1/2 in NIH3T3-flagOVA66 cells compared with NIH3T3-mock cells, while a decreased level of p-AKT and p-ERK1/2 were observed in OVA66 knocked down HeLa cells. To further validate if the p-AKT or p-ERK1/2 is essential for OVA66 induced oncogenic transformation, we treated the cells with the PI3K/AKT specific inhibitor LY294002 and the ERK1/2 MAPK specific inhibitor PD98059 and found either inhibitor can attenuate the cell colony forming ability in soft agar and the cell viability of NIH3T3-flagOVA66 cells, suggesting aberrantly activated AKT and ERK1/2 signaling be indispensible of the tumorigenic role of OVA66. Our results indicate that OVA66 is important in oncogenic transformation, promoting proliferation, cell migration and reducing apoptosis via hyperactivating PI3K/AKT and ERK1/2 MAPK signaling pathway. Thus, OVA66 might be a novel target for early detection, prevention and treatment of tumors in the future.
authors.affiliation: Shanghai Institute of Immunology, Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Rao
authors.affiliation: Department of Clinical Laboratory, Xinhua Hospital, Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai, China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Xie
authors.affiliation: Shanghai Institute of Immunology, Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Shanghai Institute of Immunology, Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai, China.
authors.forename: Shujun
authors.initials: S
authors.lastname: Wang
authors.affiliation: Shanghai Institute of Immunology, Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Shanghai Institute of Immunology, Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai, China.
authors.forename: Huizhen
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Shanghai Institute of Immunology, Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Song
authors.affiliation: Shanghai Institute of Immunology, Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai, China.
authors.forename: Renfeng
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Shanghai Institute of Immunology, Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai, China.
authors.forename: Qinqin
authors.initials: Q
authors.lastname: Yin
authors.affiliation: Department of Clinical Laboratory, Xinhua Hospital, Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai, China.
authors.forename: Lisong
authors.initials: L
authors.lastname: Shen
authors.affiliation: Shanghai Institute of Immunology, Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai, China.
authors.forename: Hailiang
authors.initials: H
authors.lastname: Ge
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D041681:NIH 3T3 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000951:Antigens, Neoplasm; D002867:Chromones; D005419:Flavonoids; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one