Upregulated expression of a unique gene by hepatitis B x antigen promotes hepatocellular growth and tumorigenesis.
Hepatitis B x antigen (HB x Ag) is a trans-activating protein that may be involved in hepatocarcinogenesis, although few natural effectors of HB x Ag that participate in this process have been identified. To identify additional effectors, whole cell RNA isolated from HB x Ag-positive and HB x Ag-negative HepG2 cells were compared by polymerase chain reaction select cDNA subtraction, and one clone, upregulated gene, clone 11 (URG11), was chosen for further characterization. Elevated levels of URG11 mRNA and protein were observed in HB x Ag-positive compared to HB x Ag-negative HepG2 cells. Costaining was observed in infected liver (P < 0.01). URG11 stimulated cell growth in culture (P < 0.01), anchorage-independent growth in soft agar (P < 0.001), and accelerated tumor formation (P < 0.01), and yielded larger tumors (P < 0.02) in SCID mice injected subcutaneously with HepG2 cells. These data suggest that URG11 is a natural effector of HB x Ag that may promote the development of hepatocellular carcinoma.
Lian
Zhaorui
Z
Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Liu
Jie
J
Li
Li
L
Li
Xianxing
X
Tufan
N Lale Satiroglu
NL
Clayton
Marcy
M
Wu
Meng-Chao
MC
Wang
Hong-Yang
HY
Arbuthnot
Patrick
P
Kew
Michael
M
Feitelson
Mark A
MA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D003001:Cloning, Molecular; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D006511:Hepatitis B Antigens / Q000502:physiology*; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D008114:Liver Neoplasms, Experimental / Q000821:virology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis*; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D006511:Hepatitis B Antigens; D012333:RNA, Messenger