A novel treatment of human malignant gliomas in vitro and in vivo: FADD gene transfer under the control of the human telomerase reverse transcriptase gene promoter

  • Authors:
    • Tadashi Komata
    • Shoji Koga
    • Satoshi Hirohata
    • Masahiro Takakura
    • Isabelle M. Germano
    • Masaki Inoue
    • Satoru Kyo
    • Seiji Kondo
    • Yasuko Kondo
  • View Affiliations

  • Published online on: November 1, 2001     https://doi.org/10.3892/ijo.19.5.1015
  • Pages: 1015-1020
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Abstract

Telomerase activity has a close relationship with malignancies in many cell types and it is tightly regulated at the transcriptional level of human telomerase reverse transcriptase (hTERT). Utilizing the hTERT promoter, the authors developed a gene delivery system of Fas associated protein with death domain (FADD) (hTERT/FADD). FADD is a protein which plays an important role in the apoptotic pathway of Fas. Over-expression of FADD induces apoptosis in the cells regardless of Fas expression on the cell surface. We hypothesized that we might be able to restrict the expression of FADD in malignant glioma cells if we use the gene transfer system under the control of hTERT promoter. This study was designed to investigate whether the hTERT/FADD construct induces apoptosis effectively in malignant glioma cells while keeping normal cells intact. First, using the reverse transcription-polymerase chain reaction (RT-PCR) technique, we confirmed that hTERT mRNA was expressed in human malignant glioma cells (U373-MG, A172 and GB-1), but not in cultured astrocytes (TEN) or fibroblasts (MRC5). After transient transfection with the hTERT/FADD construct, a significant number of FADD-positive cells and apoptotic cells were detected in hTERT-positive malignant glioma cells. In contrast, hTERT-negative astrocytes and fibroblasts remained intact. Furthermore, subcutaneously implanted U373-MG tumors treated with the hTERT/FADD construct reduced in volume significantly compared to the conrol treatment (p=0.0001). Gene transfer of FADD under the control of the hTERT promoter may be a novel and promising therapy to kill hTERT-positive malignant glioma cells while sparing normal brain cells lacking hTERT.

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November 2001
Volume 19 Issue 5

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

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Spandidos Publications style
Komata T, Koga S, Hirohata S, Takakura M, Germano IM, Inoue M, Kyo S, Kondo S and Kondo Y: A novel treatment of human malignant gliomas in vitro and in vivo: FADD gene transfer under the control of the human telomerase reverse transcriptase gene promoter. Int J Oncol 19: 1015-1020, 2001.
APA
Komata, T., Koga, S., Hirohata, S., Takakura, M., Germano, I.M., Inoue, M. ... Kondo, Y. (2001). A novel treatment of human malignant gliomas in vitro and in vivo: FADD gene transfer under the control of the human telomerase reverse transcriptase gene promoter. International Journal of Oncology, 19, 1015-1020. https://doi.org/10.3892/ijo.19.5.1015
MLA
Komata, T., Koga, S., Hirohata, S., Takakura, M., Germano, I. M., Inoue, M., Kyo, S., Kondo, S., Kondo, Y."A novel treatment of human malignant gliomas in vitro and in vivo: FADD gene transfer under the control of the human telomerase reverse transcriptase gene promoter". International Journal of Oncology 19.5 (2001): 1015-1020.
Chicago
Komata, T., Koga, S., Hirohata, S., Takakura, M., Germano, I. M., Inoue, M., Kyo, S., Kondo, S., Kondo, Y."A novel treatment of human malignant gliomas in vitro and in vivo: FADD gene transfer under the control of the human telomerase reverse transcriptase gene promoter". International Journal of Oncology 19, no. 5 (2001): 1015-1020. https://doi.org/10.3892/ijo.19.5.1015