Expression of human telomerase reverse transcriptase in regenerative and precancerous lesions of cirrhotic livers

Vassiliki Kotoula, Prodromos Hytiroglou, Athina Pyrpasopoulou, Romil Saxena, Swan N. Thung, Constantine S. Papadimitriou

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Background/Aims: The catalytic subunit of human telomerase (hTERT) is known to be expressed in a variety of malignant tumours, including hepatocellular carcinoma (HCC). We studied hTERT expression in regenerative and precancerous lesions arising in cirrhosis. Methods/Results: As shown by in situ hybridisation, hTERT mRNA was absent in normal liver, but present in varying numbers of hepatocytes and HCC cells of diseased livers, as well as in biliary epithelial cells, lymphocytes, sinusoidal-lining cells and tumour endothelial cells. RT-PCR for two hTERT transcript regions demonstrated hTERT expression in 11 out of 15 cirrhotic liver samples, in 20 out of 21 large regenerative nodules/low-grade dysplastic nodules, in 5 out of 5 high-grade dysplastic nodules, and in 4 out of 4 HCCs. The beta-splice variant was identified in all hTERT-positive cases, while the corresponding full-length transcript was found only in 13 out of 29 positive large nodular lesions and in 4 out of 11 positive cirrhotic samples. The full-length transcript was always found in the presence of the beta-splice variant, usually in low relative levels, and tended to correlate with telomerase activity in the samples, while the beta-splice variant did not. Conclusions: This study shows that hTERT re-expression takes place both in hepatic regeneration occurring in cirrhosis and in the early steps of hepatocarcinogenesis, and involves mainly the beta-splice variant of this molecule. Additional regulatory mechanisms may be required for the expression of the full-length hTERT transcript.

Original languageEnglish (US)
Pages (from-to)57-69
Number of pages13
JournalLiver
Volume22
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Telomerase
Hepatocellular Carcinoma
Liver
Fibrosis
In Situ Hybridization
Liver Diseases
Regeneration
Hepatocytes
Neoplasms
Endothelial Cells
Epithelial Cells
Lymphocytes
Polymerase Chain Reaction
Messenger RNA
human TERT protein

Keywords

  • Antisense RNA
  • Cirrhosis
  • Dysplastic nodule
  • Hepatocarcinogenesis
  • Human telomerase reverse transcriptase (hTERT)
  • In situ hybridisation
  • Regenerative nodule
  • RT-PCR
  • Splice variant

ASJC Scopus subject areas

  • Hepatology

Cite this

Expression of human telomerase reverse transcriptase in regenerative and precancerous lesions of cirrhotic livers. / Kotoula, Vassiliki; Hytiroglou, Prodromos; Pyrpasopoulou, Athina; Saxena, Romil; Thung, Swan N.; Papadimitriou, Constantine S.

In: Liver, Vol. 22, No. 1, 2002, p. 57-69.

Research output: Contribution to journalArticle

Kotoula, Vassiliki ; Hytiroglou, Prodromos ; Pyrpasopoulou, Athina ; Saxena, Romil ; Thung, Swan N. ; Papadimitriou, Constantine S. / Expression of human telomerase reverse transcriptase in regenerative and precancerous lesions of cirrhotic livers. In: Liver. 2002 ; Vol. 22, No. 1. pp. 57-69.
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AU - Hytiroglou, Prodromos

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AU - Saxena, Romil

AU - Thung, Swan N.

AU - Papadimitriou, Constantine S.

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N2 - Background/Aims: The catalytic subunit of human telomerase (hTERT) is known to be expressed in a variety of malignant tumours, including hepatocellular carcinoma (HCC). We studied hTERT expression in regenerative and precancerous lesions arising in cirrhosis. Methods/Results: As shown by in situ hybridisation, hTERT mRNA was absent in normal liver, but present in varying numbers of hepatocytes and HCC cells of diseased livers, as well as in biliary epithelial cells, lymphocytes, sinusoidal-lining cells and tumour endothelial cells. RT-PCR for two hTERT transcript regions demonstrated hTERT expression in 11 out of 15 cirrhotic liver samples, in 20 out of 21 large regenerative nodules/low-grade dysplastic nodules, in 5 out of 5 high-grade dysplastic nodules, and in 4 out of 4 HCCs. The beta-splice variant was identified in all hTERT-positive cases, while the corresponding full-length transcript was found only in 13 out of 29 positive large nodular lesions and in 4 out of 11 positive cirrhotic samples. The full-length transcript was always found in the presence of the beta-splice variant, usually in low relative levels, and tended to correlate with telomerase activity in the samples, while the beta-splice variant did not. Conclusions: This study shows that hTERT re-expression takes place both in hepatic regeneration occurring in cirrhosis and in the early steps of hepatocarcinogenesis, and involves mainly the beta-splice variant of this molecule. Additional regulatory mechanisms may be required for the expression of the full-length hTERT transcript.

AB - Background/Aims: The catalytic subunit of human telomerase (hTERT) is known to be expressed in a variety of malignant tumours, including hepatocellular carcinoma (HCC). We studied hTERT expression in regenerative and precancerous lesions arising in cirrhosis. Methods/Results: As shown by in situ hybridisation, hTERT mRNA was absent in normal liver, but present in varying numbers of hepatocytes and HCC cells of diseased livers, as well as in biliary epithelial cells, lymphocytes, sinusoidal-lining cells and tumour endothelial cells. RT-PCR for two hTERT transcript regions demonstrated hTERT expression in 11 out of 15 cirrhotic liver samples, in 20 out of 21 large regenerative nodules/low-grade dysplastic nodules, in 5 out of 5 high-grade dysplastic nodules, and in 4 out of 4 HCCs. The beta-splice variant was identified in all hTERT-positive cases, while the corresponding full-length transcript was found only in 13 out of 29 positive large nodular lesions and in 4 out of 11 positive cirrhotic samples. The full-length transcript was always found in the presence of the beta-splice variant, usually in low relative levels, and tended to correlate with telomerase activity in the samples, while the beta-splice variant did not. Conclusions: This study shows that hTERT re-expression takes place both in hepatic regeneration occurring in cirrhosis and in the early steps of hepatocarcinogenesis, and involves mainly the beta-splice variant of this molecule. Additional regulatory mechanisms may be required for the expression of the full-length hTERT transcript.

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