p53-independent increase in E2F-1 expression enhances the cytotoxic effects of etoposide and of adriamycin.

  • Authors:
    • R D Meng
    • P Phillips
    • W S El-Deiry
  • View Affiliations

  • Published online on: January 1, 1999     https://doi.org/10.3892/ijo.14.1.5
  • Pages: 5-19
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Abstract

The transcription factor E2F-1 drives cell cycle progression at the G1- to S-phase boundary; however, overexpression of E2F-1 can induce apoptosis. We show here that E2F-1 protein levels increase in human medulloblastoma, glioma, lung, colon, and bladder cancer cell lines (n=7) following treatment with the DNA damaging agents adriamycin or etoposide. This induction of E2F-1 occurs independently of Rb or p53 status and involves new protein synthesis. Although E2F-1 protein levels increase following DNA damage, several genes transcriptionally targeted by E2F-1 are not similarly induced. Rather, induction of E2F-1 in the tumor cells correlates with their sensitivity to adriamycin or to etoposide. Correspondingly, fibroblasts from E2F-1 knockout mice are more resistant to DNA damage than cells from normal mice. Overexpression of E2F-1 protein in tumor cell lines infected with an adenovirus encoding wild-type E2F-1 leads to enhanced cytotoxicity following exposure to DNA damaging agents, which results from enhanced apoptosis. The results of this study implicate a role for E2F-1 in p53-independent cytotoxicity of chemotherapy and provide a pharmacological tool for increasing levels of the apoptosis-inducing E2F-1 protein.

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Jan 1999
Volume 14 Issue 1

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

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Spandidos Publications style
Meng R, Phillips P and El-Deiry W: p53-independent increase in E2F-1 expression enhances the cytotoxic effects of etoposide and of adriamycin.. Int J Oncol 14: 5-19, 1999
APA
Meng, R., Phillips, P., & El-Deiry, W. (1999). p53-independent increase in E2F-1 expression enhances the cytotoxic effects of etoposide and of adriamycin.. International Journal of Oncology, 14, 5-19. https://doi.org/10.3892/ijo.14.1.5
MLA
Meng, R., Phillips, P., El-Deiry, W."p53-independent increase in E2F-1 expression enhances the cytotoxic effects of etoposide and of adriamycin.". International Journal of Oncology 14.1 (1999): 5-19.
Chicago
Meng, R., Phillips, P., El-Deiry, W."p53-independent increase in E2F-1 expression enhances the cytotoxic effects of etoposide and of adriamycin.". International Journal of Oncology 14, no. 1 (1999): 5-19. https://doi.org/10.3892/ijo.14.1.5