Zhang Rugang, Wang Xingwang, Guo Lixia, Xie Hong
Department of Biotherapy, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, People's Republic of China.
Int J Cancer. 2002 Jan 10;97(2):173-9. doi: 10.1002/ijc.1597.
Human hepatocellular carcinoma (HCC) is one of the most common malignancies in Asia and Africa. Human telomerase reverse transcriptase (hTERT) is expressed in HCC but absent in normal human liver cells, which is consistent with the expression pattern of telomerase. In the present study, expression of a dominant-negative form of hTERT (DN-hTERT) resulted in inhibition of telomerase activity and decreased mean telomeric length of BEL-7404 human hepatoma cells, whereas expression of wild-type hTERT (WT-hTERT) and control vector had no such effects. Cell growth was inhibited by this mutant (DN-hTERT), which was consistent with the changes in telomerase level. Flattened large cells were found in late generations with the DN-hTERT treatment. When mean telomeric length of DN-hTERT-transfected cells reached a critical length (about 1.7 kb), apoptosis was induced. Tumorigenicity of DN-hTERT-expressing cells was eliminated in vivo. These data indicated that hTERT was essential for the growth of hepatoma cells. hTERT can also be used as an important target for anti-HCC drug screening.
人类肝细胞癌（HCC）是亚洲和非洲最常见的恶性肿瘤之一。人类端粒酶逆转录酶（hTERT）在肝癌细胞中表达，但在正常人类肝细胞中不存在，这与端粒酶的表达模式一致。在本研究中，hTERT显性负性形式（DN-hTERT）的表达导致端粒酶活性受到抑制，BEL-7404人肝癌细胞的平均端粒长度缩短，而野生型hTERT（WT-hTERT）和对照载体的表达则无此效应。该突变体（DN-hTERT）抑制了细胞生长，这与端粒酶水平的变化一致。经DN-hTERT处理后，在传代后期发现细胞变为扁平的大细胞。当DN-hTERT转染细胞的平均端粒长度达到临界长度（约1.7 kb）时，诱导细胞凋亡。体内实验表明，表达DN-hTERT的细胞失去了致瘤性。这些数据表明，hTERT对肝癌细胞的生长至关重要。hTERT也可作为抗肝癌药物筛选的重要靶点。
