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

Huang,Jiayi; Shen,Lihong; Lu,Yongliang; Li,Hongli; Zhang,Xifeng; Hu,Daixi; Feng,Tao; Song,Fangzhou

doi:10.3892/ijmm.2012.1060

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

Authors:
- Jiayi Huang
- Lihong Shen
- Yongliang Lu
- Hongli Li
- Xifeng Zhang
- Daixi Hu
- Tao Feng
- Fangzhou Song
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Affiliations: Molecular Medicine and Cancer Research Center, Chongqing 400016, P.R. China
Published online on: July 12, 2012 https://doi.org/10.3892/ijmm.2012.1060
Pages: 842-848

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Abstract

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.

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