Hepatitis Bx antigen stimulates expression of a novel cellular gene, URG4, that promotes hepatocellular growth and survival.
Hepatitis B virus encoded X antigen (HBxAg) may contribute to the development of hepatocellular carcinoma (HCC) by up- or downregulating the expression of cellular genes that promote cell growth and survival. To test this hypothesis, HBxAg-positive and -negative HepG2 cells were constructed, and the patterns of cellular gene expression compared by polymerase chain reaction select cDNA subtraction. The full-length clone of one of these upregulated genes (URG), URG4, encoded a protein of about 104 kDa. URG4 was strongly expressed in hepatitis B-infected liver and in HCC cells, where it costained with HBxAg, and was weakly expressed in uninfected liver, suggesting URG4 was an effector of HBxAg in vivo. Overexpression of URG4 in HepG2 cells promoted hepatocellular growth and survival in tissue culture and in soft agar, and accelerated tumor development in nude mice. Hence, URG4 may be a natural effector of HBxAg that contributes importantly to multistep hepatocarcinogenesis.
Tufan
N Lale Satiroglu
NL
Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107-6799, USA.
Lian
Zhaorui
Z
Liu
Jie
J
Pan
Jingbo
J
Arbuthnot
Patrick
P
Kew
Michael
M
Clayton
Marcy M
MM
Zhu
Minghua
M
Feitelson
Mark A
MA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D006509:Hepatitis B / Q000150:complications; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology*; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D009368:Neoplasm Transplantation; D009928:Organ Specificity; D010183:Pancreatic Ducts / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000637:transplantation; D014412:Tumor Virus Infections / Q000150:complications; D014760:Viral Fusion Proteins / Q000502:physiology*
D018076:DNA, Complementary; D009363:Neoplasm Proteins; C470990:URGCP protein, human; D014760:Viral Fusion Proteins; C063377:X antigen, viral infections