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Activated ras oncogene collaborates with HBx gene of hepatitis B virus to transform cells by suppressing HBx-mediated apoptosis

Authors
 Young Chul Kim  ;  Kyung-Seob Song  ;  Gyesoon Yoon  ;  Myeong-Jin Nam  ;  Wang-Shick Ryu 
Citation
 ONCOGENE, Vol.20(1) : 16-23, 2001 
Journal Title
ONCOGENE
ISSN
 0950-9232 
Issue Date
2001
MeSH
3T3 Cells ; Animals ; Apoptosis/genetics* ; Cell Line ; Cell Line, Transformed ; Cell Transformation, Neoplastic/genetics* ; Cell Transformation, Viral/genetics* ; Embryo, Mammalian ; Gene Expression Regulation, Neoplastic* ; Gene Expression Regulation, Viral* ; Genes, Suppressor ; Genes, Viral ; Genes, ras* ; Hepatitis B virus/genetics* ; Mice ; Phosphatidylinositol 3-Kinases/physiology ; Protein-Serine-Threonine Kinases* ; Protein-Tyrosine Kinases/physiology ; Proto-Oncogene Proteins/physiology ; Proto-Oncogene Proteins c-akt ; Rats ; Signal Transduction/genetics ; Trans-Activators/genetics* ; Transfection ; Viral Structural Proteins/genetics
Keywords
hepatitis B virus ; X gene ; apoptosis ; H-ras oncogene
Abstract
The hepatitis B virus HBx protein is a promiscuous transactivator implicated in the development of hepatocellular carcinoma. The ectopic expression of HBx fails to transform both primary and immortalized rodent cells, but rather induces apoptosis. Furthermore, most transgenic mice harboring HBx do not develop liver tumors. Thus, it remains unclear whether and how HBx contributes to oncogenesis. Here, we show that HBx collaborates with activated H-ras to transform immortalized rodent cells. Indeed, REF52 cells transfected by both HBx and activated H-ras were morphologically transformed and were able to grow in soft agar. Remarkably, nude mice injected with REF52 cells transfected by both HBx and activated H-ras developed tumors, whereas the mice injected with REF52 cells transfected by either gene alone did not. Thus, we concluded that HBx could contribute to neoplastic transformation of cells in collaboration with other oncogenes, such as H-ras, that renders cells to overcome the HBx-mediated apoptosis. Further, we found that HBx mediated apoptosis was suppressed by activated H-ras through activation of the phosphatidylinositol-3 kinase and Akt pathway. Data presented here firmly established the oncogenic potential of HBx during multistage carcinogenesis.
Files in This Item:
T200103241.pdf Download
DOI
10.1038/sj.onc.1203840
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
Yonsei Authors
Song, Kyoung Seob(송경섭)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/142890
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