Pro-oncogenic potential of NM23-H2 in hepatocellular carcinoma.
10.3858/emm.2012.44.3.016
- Author:
Mi Jin LEE
1
;
Dong Yuan XU
;
Hua LI
;
Goung Ran YU
;
Sun Hee LEEM
;
In Sun CHU
;
In Hee KIM
;
Dae Ghon KIM
Author Information
1. 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. daeghon@chonbuk.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
carcinogenecity tests;
carcinoma, hepatocellular;
cell transformation, neoplastic;
NM23 nucleoside diphosphate kinases;
oncogenes;
protooncogene proteins c-myc
- MeSH:
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
- From:Experimental & Molecular Medicine
2012;44(3):214-224
- CountryRepublic of Korea
- Language:English
-
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.