The absence of up-regulation of telomerase activity during regeneration after partial hepatectomy in hepatitis B virus X gene transgenic mice

Hiroshige Kojima, Kelly D.E. Kaita, Zhenming Xu, James H. Ou, Yuewen Gong, Manna Zhang, Gerald Y. Minuk

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background/Aims: 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.

Original languageEnglish (US)
Pages (from-to)262-268
Number of pages7
JournalJournal of Hepatology
Volume39
Issue number2
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

Fingerprint

Telomerase
Hepatectomy
Hepatitis B virus
Transgenic Mice
Regeneration
Up-Regulation
Genes
Human Activities
Messenger RNA
Transfection
Hepatocytes
hepatitis B virus X protein
Reverse Transcription
Carcinogenesis
Complementary DNA
Polymerase Chain Reaction

Keywords

  • HBV X protein
  • Hepatitis B
  • Hepatocellular carcinoma
  • Murine telomerase reverse transcriptase
  • Telomerase
  • Telomere
  • Transgenic mice

ASJC Scopus subject areas

  • Hepatology

Cite this

The absence of up-regulation of telomerase activity during regeneration after partial hepatectomy in hepatitis B virus X gene transgenic mice. / Kojima, Hiroshige; Kaita, Kelly D.E.; Xu, Zhenming; Ou, James H.; Gong, Yuewen; Zhang, Manna; Minuk, Gerald Y.

In: Journal of Hepatology, Vol. 39, No. 2, 01.08.2003, p. 262-268.

Research output: Contribution to journalArticle

Kojima, Hiroshige ; Kaita, Kelly D.E. ; Xu, Zhenming ; Ou, James H. ; Gong, Yuewen ; Zhang, Manna ; Minuk, Gerald Y. / The absence of up-regulation of telomerase activity during regeneration after partial hepatectomy in hepatitis B virus X gene transgenic mice. In: Journal of Hepatology. 2003 ; Vol. 39, No. 2. pp. 262-268.
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abstract = "Background/Aims: 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.",
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AU - Xu, Zhenming

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AU - Gong, Yuewen

AU - Zhang, Manna

AU - Minuk, Gerald Y.

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N2 - Background/Aims: 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.

AB - Background/Aims: 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.

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KW - Hepatitis B

KW - Hepatocellular carcinoma

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KW - Telomere

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