title: Pro-oncogenic potential of NM23-H2 in hepatocellular carcinoma.
abstract: NM23 is a family of structurally and functionally conserved proteins known as nucleoside diphosphate kinases (NDPK). There is abundant mRNA expression of NM23-H1, NM23-H2, or a read through transcript (NM23-LV) in the primary sites of hepatocellular carcinoma (HCC). Although the NM23-H1 protein is implicated as a metastasis suppressor, the role of NM23-H2 appears to be less understood. Thus, the aim of this study was to examine whether NM23-H2 is associated with hepatocarcinogenesis. The level of NM23-H2 expression in tumor tissues and the surrounding matrix appeared to be independent of etiology and tumor differentiation. Its subcellular localization was confined to mainly the cytoplasm and to a lesser extent in the nucleus. Ectopic expression of NM23-H2 in NIH3T3 fibroblasts and HLK3 hepatocytes showed a transformed morphology, enhanced focus formation, and allowed anchorage-independent growth. Finally, NIH3T3 fibroblasts and HLK3 hepatocytes stably expressing NM23-H2 produced tumors in athymic mice and showed c-Myc over-expression. In addition, NF-κB and cyclin D1 expression were also increased by NM23-H2. Lentiviral delivery of NM23-H2 shRNA inhibited tumor growth of xenotransplanted tumors produced from HLK3 cells stably expressing NM23-H2. Collectively, these results indicate that NM23-H2 may be pro-oncogenic in hepatocarcinogenesis.
authors.affiliation: Division of GI and Hepatology, The Research Institute of Clinical Medicine, Department of Internal Medicine, Chonbuk National University Medical School and Hospital, Jeonju 561-712, Korea.
authors.forename: Mi-Jin
authors.initials: MJ
authors.lastname: Lee
authors.forename: Dong-Yuan
authors.initials: DY
authors.lastname: Xu
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Goung-Ran
authors.initials: GR
authors.lastname: Yu
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Leem
authors.forename: In-Sun
authors.initials: IS
authors.lastname: Chu
authors.forename: In-Hee
authors.initials: IH
authors.lastname: Kim
authors.forename: Dae-Ghon
authors.initials: DG
authors.lastname: Kim
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008099:Liver / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D054778:NM23 Nucleoside Diphosphate Kinases