Functional Interplay Between E2F1 and Chemotherapeutic Drugs Defines Immediate E2F1 Target Genes Crucial for Cancer Cell Death

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2009 Dec 17

PMID 20013022

Citations 10

Authors

David Engelmann

Susanne Knoll

Daniel Ewerth

Marc Steder

Anja Stoll

Brigitte M Putzer

Affiliations

Soon will be listed here.

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.

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