Exp Mol Med.  2012 Mar;44(3):214-224. 10.3858/emm.2012.44.3.016.

Pro-oncogenic potential of NM23-H2 in hepatocellular carcinoma

• Lee MJ
• Xu DY
• Li H
• Yu GR
• Leem SH
• Chu IS
• Kim IH
• Kim DG

• KMID: 1245264
• DOI: http://doi.org/10.3858/emm.2012.44.3.016

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-kappaB 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.

Keyword

carcinogenecity tests; carcinoma, hepatocellular; cell transformation, neoplastic; NM23 nucleoside diphosphate kinases; oncogenes; protooncogene proteins c-myc

MeSH Terms

Animals
Carcinoma, Hepatocellular/*enzymology/genetics/pathology
Cell Line
Cell Line, Tumor
*Gene Expression Regulation, Neoplastic
Humans
Liver/*enzymology/metabolism/pathology
Liver Neoplasms/*enzymology/genetics/pathology
Mice
Mice, Nude
NIH 3T3 Cells
NM23 Nucleoside Diphosphate Kinases/*genetics/metabolism