Expression of hepatitis B virus X (HBx) gene is up-regulated by adriamycin at the post-transcriptional level.
Hepatitis B virus (HBV) X protein (HBx) is thought to be involved in the development of liver cancer and alteration of cellular HBx level may influence the pathological progression of HBV-induced liver diseases. We found that the cellular levels of HBx mRNA transcript and protein in cells were greatly enhanced by adriamycin, a topoisomerase II inhibitor. Up-regulation of HBx mRNA by adriamycin was also observed in HBx transgenic mice, which was accompanied with a significant increase of VEGF mRNA, the downstream target of HBx. When we investigated the underlying mechanism, we found that half-life of HBx mRNA in HBx-expressing Chang cells was about 3h, but was prolonged to >6h in the presence of adriamycin. Moreover, half-life of rapidly degrading HBx protein was determined as about 15min however, it remained almost constant until 60min in the presence of adriamycin. These results provide the first evidence that the cellular level of HBx gene can be increased at the post-transcriptional level.
Department of Biochemistry, Ajou University School of Medicine, 5 Wonchon-dong, Paldal-ku, 442-749, Suwon, Republic of Korea.
Chawon
C
Yun
Jae-Ho
JH
Lee
Jin-Hee
JH
Wang
Je Kyung
JK
Seong
Seung Hyun
SH
Oh
Dae-Yeul
DY
Yu
Hyeseong
H
Cho
D000818:Animals; D002460:Cell Line; D004317:Doxorubicin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D059005:Topoisomerase II Inhibitors; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic; D015854:Up-Regulation; D054334:Viral Regulatory and Accessory Proteins
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D012367:RNA, Viral; D059005:Topoisomerase II Inhibitors; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D004317:Doxorubicin