Gene therapy for prostate cancer targeting transcription factor E2F/DRTF

  • Authors:
    • M Lee
    • M Liu
    • C Lee
  • View Affiliations

  • Published online on: April 1, 1997     https://doi.org/10.3892/ijo.10.4.729
  • Pages: 729-734
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Abstract

The heterodimeric transcription factor E2F/DRTF plays a key role in integrating the transactivation of DNA replication-associated genes with cell cycle progression. Strictly regulated in a tissue-specific manner, the prostate-specific antigen promoter (PSAP) can be used to direct prostate-specific gene therapy. Employing PSAP and taking advantage of dominant negative suppression and antisense counteraction, we constructed three PSAP-driven plasmids targeting E2F/DRTF: PSAP-E2FL, PSAP-E2FS, and PSAP-antiE2F-1, which, upon induction, would express two truncated E2F-1 proteins lacking the DNA-binding domain and an antisense E2F-1 transcript. Lipofection-mediated gene transfers were performed in three prostate cancer cell lines (DU-145, PC-3 and LNCaP) and six cell lines of other origin (HL-60, KG-1: Hep G2, Cos-l, NCI H460, and SW480). In DU-145, PC-3, and LNCaP, PSAP-E2FL exhibited a growth inhibition of >99%, 94.8%, and 36.9%, respectively; PSAP-E2FS induced growth inhibition at 48.3%, 43.7%, and 34%; PSAP-antiE2F-1 suppressed the growth by 9.5%, 16.3%, and 46.8%. None of these constructs showed significant growth inhibition in cells of hematopoietic (HL-60, KG-1), hepatic (Hep G2), renal (Cos-l), pulmonary (NCI H460) or colon (SW480) origin. Examination on DU-145 transfectants by RT-PCR revealed that PSAP-E2FL suppressed the expression of c-myc and DNA polymerase-alpha by 82.5% and 65.8%, respectively. The inhibition of DNA synthesis was further confirmed by an ill situ BrdU incorporation analysis in DU-145 and PC-3 transfectants. Without damaging other cells, the PSAP-driven genetic constructs targeting E2F/DRTF proved to be potent in inducing tissue-specific cytotoxicity solely in cells of prostate origin.

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April 1997
Volume 10 Issue 4

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

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Spandidos Publications style
Lee M, Liu M and Lee C: Gene therapy for prostate cancer targeting transcription factor E2F/DRTF. Int J Oncol 10: 729-734, 1997
APA
Lee, M., Liu, M., & Lee, C. (1997). Gene therapy for prostate cancer targeting transcription factor E2F/DRTF. International Journal of Oncology, 10, 729-734. https://doi.org/10.3892/ijo.10.4.729
MLA
Lee, M., Liu, M., Lee, C."Gene therapy for prostate cancer targeting transcription factor E2F/DRTF". International Journal of Oncology 10.4 (1997): 729-734.
Chicago
Lee, M., Liu, M., Lee, C."Gene therapy for prostate cancer targeting transcription factor E2F/DRTF". International Journal of Oncology 10, no. 4 (1997): 729-734. https://doi.org/10.3892/ijo.10.4.729