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Pro-oncogenic potential of NM23-H2 in hepatocellular carcinoma
- Source :
- Experimental & Molecular Medicine
- Publication Year :
- 2011
- Publisher :
- Korean Society for Biochemistry and Molecular Biology, 2011.
-
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.
- Subjects :
- Carcinoma, Hepatocellular
oncogenes
Clinical Biochemistry
Mice, Nude
Biology
Biochemistry
Cell Line
Small hairpin RNA
Mice
Cyclin D1
Cell Line, Tumor
protooncogene proteins c-myc
Animals
Humans
Metastasis suppressor
Molecular Biology
cell transformation, neoplastic
Kinase
Liver Neoplasms
NM23 Nucleoside Diphosphate Kinases
Subcellular localization
Molecular biology
Gene Expression Regulation, Neoplastic
carcinogenecity tests
Liver
Cell culture
Cytoplasm
Cancer research
NIH 3T3 Cells
Molecular Medicine
Ectopic expression
Original Article
Subjects
Details
- Language :
- English
- ISSN :
- 20926413 and 12263613
- Volume :
- 44
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Experimental & Molecular Medicine
- Accession number :
- edsair.doi.dedup.....545c730dc715b389b6c38e4695b85b43