Parallel induction of cell proliferation and inhibition of cell differentiation in hepatic progenitor cells by hepatitis B virus X gene

Increasing evidence has shown that normal stem cells may contribute to the development and progression of cancer by acting as cancer-initiating cells. The hepatitis B virus X (HBX) protein has been implicated in the hepatitis B virus (HBV)-associated liver carcinogenesis. However, the role of HBX in...

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Bibliographic Details
Published in:International journal of molecular medicine 2012-10, Vol.30 (4), p.842-848
Main Authors: HUANG, JIAYI, SHEN, LIHONG, LU, YONGLIANG, LI, HONGLI, ZHANG, XIFENG, HU, DAIXI, FENG, TAO, SONG, FANGZHOU
Format: Article
Language:English
Subjects:
Adenoviruses
Antigens
Apoptosis
cancer stem cells
Cell culture
Cell cycle
Cell growth
Genomes
hepatic differentiation
hepatic progenitor cells
Hepatitis
Hepatitis B
hepatitis B virus X
hepatocellular carcinoma
Liver cancer
Medical research
Mutation
Proteins
Rodents
Signal transduction
Stem cells
Studies
Transgenic animals
Tumorigenesis
Tumors
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Summary:Increasing evidence has shown that normal stem cells may contribute to the development and progression of cancer by acting as cancer-initiating cells. The hepatitis B virus X (HBX) protein has been implicated in the hepatitis B virus (HBV)-associated liver carcinogenesis. However, the role of HBX in hepatic progenitor cells (HPCs) is poorly understood. In this study, we aimed to determine the role of HBX in regulating HPC proliferation and differentiation. Using MTT analysis, we showed that HPCs infected with adenovirus expressing HBX (Ad-HBX) grew more rapidly compared to HPCs infected with adenovirus expressing green fluorescent protein (Ad-GFP). To reveal the mechanism for the increased cell number after HBX treatment, we searched for possible alterations in the cell cycle and apoptosis by flow cytometry. We found that HBX treatment resulted in an increase in the S phase cell cycle fraction and a decrease in apoptosis. In addition, we examined the differentiation of HPCs infected with Ad-HBX and found that the HBX expression in HP14.5 cells led to an increased expression of early progenitor markers and a decreased expression of late hepatocyte markers. Furthermore, HBX inhibited glycogen synthesis in HP14.5 cells, indicating that HBX is capable of inhibiting terminal hepatic differentiation. Therefore, our results strongly suggest that HBX plays an important role in regulating HPC proliferation and differentiation. This is the potential mechanism of HBX-mediated liver carcinogenesis.
ISSN:1107-3756
1791-244X
DOI:10.3892/ijmm.2012.1060