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


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.
Kotoula
Vassiliki
V
Department of Pathology, Aristotle University Medical School, Thessaloniki, Greece.
Hytiroglou
Prodromos
P
Pyrpasopoulou
Athina
A
Saxena
Romil
R
Thung
Swan N
SN
Papadimitriou
Constantine S
CS
D000293:Adolescent; D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins; D005260:Female; D020518:Focal Nodular Hyperplasia / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D017403:In Situ Hybridization; D008103:Liver Cirrhosis / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000201:enzymology* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019098:Telomerase