The absence of up-regulation of telomerase activity during regeneration after partial hepatectomy in hepatitis B virus X gene transgenic mice.
OBJECTIVE
Transgenic mice that express HBV X protein (HBx) have increased sensitivity to hepatocarcinogens. In the present study, we hypothesized that HBx interferes with the DNA protective increases in telomerase activity that occur in proliferating hepatocytes.


METHODS
Male CD-1 mice (4-6/grp) were killed and hepatic telomerase activity measured at 0, 6, 12, 24, 36, 48 h post partial hepatectomy (PHx). Four HBx transgenic mice were killed at 12 h post-PHx when maximum telomerase activity was observed in CD-1 non-transgenic mice. mRNA of the telomerase catalytic subunit; murine telomerase reverse transcriptase (mTERT), was measured by reverse transcription-polymerase chain reaction. Telomerase activity and human TERT (hTERT) were also measured in Chang and PLC/PRF/5 cells following transient transfection with HBx cDNA.


RESULTS
Telomerase activity peaked at 12 h post-PHx in normal mice, however, in HBx transgenic mice, telomerase activity was significantly lower, both at baseline (P<0.05) and 12 h post-PHx (P<0.01). Following PHx, mTERT mRNA expression remained constant in normal mice but decreased significantly (P<0.01) in HBx transgenic mice. Transfection of HBx in Chang and PLC/PRF/5 cells had no effect on telomerase activity or hTERT mRNA expression.


CONCLUSIONS
The results of this study suggest that HBx expression may play a role in hepatocellular carcinogenesis by interfering with telomerase activity during hepatocyte proliferation.
Kojima
Hiroshige
H
Section of Hepatology, Department of Medicine, University of Manitoba, Winnipeg, Man., Canada.
Kaita
Kelly D E
KD
Xu
Zhenming
Z
Ou
James H
JH
Gong
Yuewen
Y
Zhang
Manna
M
Minuk
Gerald Y
GY
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000503:physiopathology; D004268:DNA-Binding Proteins; D006498:Hepatectomy; D008113:Liver Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics*; D014162:Transfection; D015854:Up-Regulation; D054334:Viral Regulatory and Accessory Proteins
D004268:DNA-Binding Proteins; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; C509186:TERT protein, human; D019098:Telomerase; C509187:Tert protein, mouse