[Expressions of hepatitis B virus x protein and hypoxia-inducible factor-1alpha in hepatocellular carcinoma and their possible relationships].
OBJECTIVE
To investigate the expressions of hepatitis B virus x protein (HBx) and hypoxia-inducible factor-1alpha (HIF-1alpha) in hepatocellular carcinoma (HCC) tissues and HepG2 cells under normoxic and hypoxic conditions.


METHODS
Immunohistochemistry was used to detect the expressions of HBx and HIF-1alpha in 78 hepatic carcinoma tissues, and their possible relationships were analyzed using SPSS 10.0 statistical software. Immunofluorescence and Western blot were used to investigate the expression of HIF-1alpha in HepG2 and HepG2-X cells under normoxic and hypoxic conditions. Flow cytometric analysis was used to measure reactive oxygen species (ROS) in HepG2 and HepG2-Xd cells under normoxic and hypoxic conditions.


RESULTS
The positive rate of HBx in the hepatocellular carcinoma tissues was 74.36% (58/78), while the positive rate of HIF-1alpha was 69.23% (54/78). Under normoxic condition, HIF-1alpha was mainly localized in the cytoplasm and partially translocated into the nuclei of most HepG2-X cells, while under hypoxic condition the expression of HIF-1alpha was positive in the cytoplasm and nuclei of HepG2 and HepG2-X cells. Under normoxic condition the expression of HIF-1alpha was negative in the HepG2 cells while it was positive in HepG2-X cells, but HIF-1alpha was upregulated time-dependently in both HepG2 and HepG2-X cells under hypoxia condition. Furthermore, HepG2-X cells had a higher level of ROS than HepG2 cells under normoxic condition, while under hypoxic condition, the levels of ROS in HepG2 and HepG2-X cells were not significantly different, but the levels of ROS in HepG2 and HepG2-X cells under hypoxia condition were higher than those under normoxia condition.


CONCLUSIONS
HBx and HIF-1alpha were widely expressed in HCC tissues and there is a positive relationship between them. HIF-1alpha can be upregulated by HBx in HepG2 cells under normoxic and hypoxia conditions. Regulation of HIF-1alpha by HBx in HCC might be via the ROS pathway.
Liu
Kai-ge
KG
Affiliated Hospital of Xi'an Medical College, Xi'an 710077, China. kaigeliu@gmail.com
Xie
Hua-hong
HH
Liu
Jie
J
D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D056945:Hep G2 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein