Cancer-specific killing by the CD suicide gene using the human telomerase reverse transcriptase promoter

  • Authors:
    • Jing Liu
    • Wei-Guo Zou
    • Ming-Fei Lang
    • Jia Luo
    • Lan-Ying Sun
    • Xiao-Ning Wang
    • Qi-Jun Qian
    • Xin-Yuan Liu
  • View Affiliations

  • Published online on: September 1, 2002     https://doi.org/10.3892/ijo.21.3.661
  • Pages: 661-666
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Abstract

Human telomerase reverse transcriptase (hTERT), the catalytic subunit of the telomerase, is transcriptionally upregulated in more than 90% of tumor cells. It may be used as a tool for driving a gene to kill tumors specifically. To test this idea, luciferase reporter gene was used and the results showed that hTERT promoter could restrict the gene expression in the telomerase-positive tumor cells. A tumor-specific expression plasmid phTERT-CD was constructed, in which the E. coli cytosine deaminase (CD) gene was controlled by the hTERT promoter. A colorectal cancer cell line (LoVo) and a normal amnion cell line (WISH) were transfected by this plasmid. It was shown that the expression of the CD gene increased the sensitivity of LoVo cells to the prodrug, 5-fluorocytosine (5FC), over 800-fold, while the sensitivity of WISH cells to 5FC was increased only 6-fold. Mixed cell experiments showed a strong on CD-negative cells. Furthermore, a significant anti-tumor effect of the phTERT-CD/5FC system was observed in nude mice bearing mammalian carcinoma induced by s.c. inoculation of LoVo cells when the mice were given 250 mg/kg 5FC twice a day for 10 consecutive days. These results indicated that hTERT promoter could target the suicidal effect of CD gene to tumor cells, and therefore, may be a novel and promising targeting approach to the treatment of cancer.

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September 2002
Volume 21 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Liu J, Zou W, Lang M, Luo J, Sun L, Wang X, Qian Q and Liu X: Cancer-specific killing by the CD suicide gene using the human telomerase reverse transcriptase promoter. Int J Oncol 21: 661-666, 2002
APA
Liu, J., Zou, W., Lang, M., Luo, J., Sun, L., Wang, X. ... Liu, X. (2002). Cancer-specific killing by the CD suicide gene using the human telomerase reverse transcriptase promoter. International Journal of Oncology, 21, 661-666. https://doi.org/10.3892/ijo.21.3.661
MLA
Liu, J., Zou, W., Lang, M., Luo, J., Sun, L., Wang, X., Qian, Q., Liu, X."Cancer-specific killing by the CD suicide gene using the human telomerase reverse transcriptase promoter". International Journal of Oncology 21.3 (2002): 661-666.
Chicago
Liu, J., Zou, W., Lang, M., Luo, J., Sun, L., Wang, X., Qian, Q., Liu, X."Cancer-specific killing by the CD suicide gene using the human telomerase reverse transcriptase promoter". International Journal of Oncology 21, no. 3 (2002): 661-666. https://doi.org/10.3892/ijo.21.3.661