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

被引:42
作者
Kotoula, V
Hytiroglou, P [1 ]
Pyrpasopoulou, A
Saxena, R
Thung, SN
Papadimitriou, CS
机构
[1] Aristotle Univ, Med Sch, Dept Pathol, Thessaloniki 54006, Greece
[2] Mt Sinai Sch Med, Hans Popper Dept Pathol, New York, NY USA
来源
LIVER | 2002年 / 22卷 / 01期
关键词
antisense RNA; cirrhosis; dysplastic nodule; hepatocarcinogenesis; human telomerase reverse transcriptase; (hTERT); in situ hybridisation; regenerative nodule; RT-PCR; splice variant;
D O I
10.1046/j.0106-9543.2001.01594.x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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 I I 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.
引用
收藏
页码:57 / 69
页数:13
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