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 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.
Molecular Medicine and Cancer Research Center, Chongqing 400016, PR China.
Jiayi
J
Huang
Lihong
L
Shen
Yongliang
Y
Lu
Hongli
H
Li
Xifeng
X
Zhang
Daixi
D
Hu
Tao
T
Feng
Fangzhou
F
Song
D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D002472:Cell Transformation, Viral; D056945:Hep G2 Cells; D006509:Hepatitis B / Q000150:complications / Q000821:virology; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000473:pathology* / Q000821:virology*; D008113:Liver Neoplasms / Q000821:virology; D013234:Stem Cells / Q000166:cytology / Q000821:virology*; D015534:Trans-Activators / Q000235:genetics*; D054334:Viral Regulatory and Accessory Proteins
D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein