Pro-oncogenic potential of NM23-H2 in hepatocellular carcinoma

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Pro-oncogenic potential of NM23-H2 in hepatocellular carcinoma
M J Lee; D Y Xu; H Li; G R Yu; S H Leem; In-Sun Chu; I H Kim; D G Kim
Bibliographic Citation
Experimental and Molecular Medicine, vol. 44, no. 3, pp. 214-224
Publication Year
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.
Carcinogenecity testsCarcinomaCell transformationHepatocellularNeoplasticNM23 nucleoside diphosphate kinasesOncogenesProtooncogene proteins c-myc
Springer-Nature Pub Group
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Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
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