FADD gene therapy using the human telomerase catalytic subunit (hTERT) gene promoter to restrict induction of apoptosis to tumors in vitro and in vivo

S. Koga, Satoshi Hirohata, Y. Kondo, T. Komata, M. Takakura, M. Inoue, S. Kyo, S. Kondo

Research output: Contribution to journalArticle

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Abstract

Gene transfer vectors will dramatically increase the safety and effectiveness of cancer gene therapy, if they could restrict expression of the therapeutic products to the target tumors. To realize such a tumor-targeting system, telomerase is one of the most promising candidates. It is because telomerase activity is detected in the vast majority of tumors, but not in most normal cells. Activation of telomerase is tightly regulated at the transcriptional level of the telomerase catalytic subunit (hTERT). Therefore, the use of the hTERT promoter-driven vector system could restrict the expression of therapeutic products to telomerase-positive tumors. In this study, we constructed the expression vector of FADD gene with death domain afforded by the hTERT promoter (hTERT/FADD) and investigated its effect on tumors in vitro and in vivo. Transient transfection with the hTERT/FADD construct induced apoptosis in telomerase-positive tumor cells of wide range. In contrast, normal fibroblast cells without telomerase did not undergo apoptosis following the hTERT/FADD transfer. Furthermore, the growth of subcutaneous tumors in nude mice was significantly suppressed by the intratumoral injection of the hTERT/FADD construct (every day for one week) compared to the control (P

Original languageEnglish
Pages (from-to)1937-1943
Number of pages7
JournalAnticancer Research
Volume21
Issue number3 B
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Telomerase
Genetic Therapy
Apoptosis
Genes
Neoplasms
In Vitro Techniques
Neoplasm Genes
Nude Mice
Transfection

Keywords

  • Apoptosis
  • FADD
  • Gene therapy
  • hTERT promoter
  • Telomerase

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

FADD gene therapy using the human telomerase catalytic subunit (hTERT) gene promoter to restrict induction of apoptosis to tumors in vitro and in vivo. / Koga, S.; Hirohata, Satoshi; Kondo, Y.; Komata, T.; Takakura, M.; Inoue, M.; Kyo, S.; Kondo, S.

In: Anticancer Research, Vol. 21, No. 3 B, 2001, p. 1937-1943.

Research output: Contribution to journalArticle

Koga, S. ; Hirohata, Satoshi ; Kondo, Y. ; Komata, T. ; Takakura, M. ; Inoue, M. ; Kyo, S. ; Kondo, S. / FADD gene therapy using the human telomerase catalytic subunit (hTERT) gene promoter to restrict induction of apoptosis to tumors in vitro and in vivo. In: Anticancer Research. 2001 ; Vol. 21, No. 3 B. pp. 1937-1943.
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