Growth inhibition of BEL-7404 human hepatoma cells by expression of mutant telomerase reverse transcriptase.
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.
Zhang
Rugang
R
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.
Wang
Xingwang
X
Guo
Lixia
L
Xie
Hong
H
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D002455:Cell Division / Q000502:physiology; D004268:DNA-Binding Proteins; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D012333:RNA, Messenger / Q000096:biosynthesis; D019098:Telomerase / Q000502:physiology*; D016615:Telomere / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D019098:Telomerase