An intracellular antibody can suppress tumorigenicity in hepatitis B virus X-expressing cells.
Although the hepatitis B virus X protein (HBx) is thought to play a causative role in the development of hepatocellular carcinoma, it is not yet known whether interfering with HBx function may affect the cellular transformation of HBx-expressing tumor cells. To address this question, we adopted an intracellular antibody fragment expression approach to block the function of HBx. Expression of a single-chain variable fragment (scFv) specific to HBx (designated as H7scFv) inhibited HBx-dependent cellular transactivation. Furthermore, H7scFv suppressed the growth of HBx-expressing tumor cells in both soft agar and nude mice. The suppressive effect of H7scFv on tumorigenicity appeared not to be mediated by inhibition of HBx-induced growth stimulation since the growth rate of these cells was not affected significantly by H7scFv expression. In conclusion, these data suggest that the HBx-dependent transformed phenotype is reversible and that HBx may be a good molecular target for the treatment of HBV-related tumors.
Jin
Young-Hee
YH
Department of Microbiology, Ajou University School of Medicine, San 5 wonchun-dong yeongtong-gu, Suwon, 442-749, Republic of Korea.
Kwon
Myung-Hee
MH
Kim
Kyongmin
K
Shin
Ho Joon
HJ
Shin
Jeon-Soo
JS
Cho
Hyeseong
H
Park
Sun
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000821:virology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D003593:Cytoplasm / Q000276:immunology; D005455:Fluorescent Antibody Technique; D007128:Immunoglobulin Fragments / Q000276:immunology*; D047468:Immunoprecipitation; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism / Q000821:virology; D051379:Mice; D041681:NIH 3T3 Cells; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000276:immunology / Q000378:metabolism*; D015533:Transcriptional Activation; D054334:Viral Regulatory and Accessory Proteins
D000911:Antibodies, Monoclonal; D007128:Immunoglobulin Fragments; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein