Cellular and Molecular Life Sciences

, Volume 67, Issue 6, pp 931–948

Functional interplay between E2F1 and chemotherapeutic drugs defines immediate E2F1 target genes crucial for cancer cell death

  • David Engelmann
  • Susanne Knoll
  • Daniel Ewerth
  • Marc Steder
  • Anja Stoll
  • Brigitte M. Pützer
Research Article

Abstract

The E2F1 transcription factor enhances apoptosis by DNA damage in tumors lacking p53. To elucidate the mechanism of a potential cooperation between E2F1 and chemotherapy, whole-genome microarrays of chemoresistant tumor cell lines were performed focusing on the identification of cooperation response genes (CRG). This gene class is defined by a synergistic expression response upon endogenous E2F1 activation and drug treatment. Cluster analysis revealed an expression pattern of CRGs similar to E2F1 mono-therapy, suggesting that chemotherapeutics enhance E2F1-dependent gene expression at the transcriptional level. Using this approach as a tool to explore E2F1-driven gene expression in response to anticancer drugs, we identified novel apoptosis genes such as the tumor suppressor TIEG1/KLF10 as direct E2F1 targets. We show that TIEG1/KLF10 is transcriptionally activated by E2F1 and crucial for E2F1-mediated chemosensitization of cancer cells. Our results provide a broader picture of E2F1-regulated genes in conjunction with cytotoxic treatment that allows the design of more rational therapeutics.

Keywords

E2F1 Chemotherapy Cooperation response genes TIEG1/KLF10 Cell death Cancer 

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Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2009

Authors and Affiliations

  • David Engelmann
    • 1
  • Susanne Knoll
    • 1
  • Daniel Ewerth
    • 1
  • Marc Steder
    • 1
  • Anja Stoll
    • 1
  • Brigitte M. Pützer
    • 1
  1. 1.Department of Vectorology and Experimental Gene Therapy, Biomedical Research CenterUniversity of RostockRostockGermany

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