E2F1 drives chemotherapeutic drug resistance via ABCG2

Mathias Rosenfeldt, Laura Bell, Jaclyn Long, Jim O'Prey, Colin Nixon, Fiona Roberts, Christine Dufès, Kevin Ryan

Research output: Contribution to journalArticle

  • 17 Citations

Abstract

Multidrug resistance is a major barrier against successful chemotherapy, and this has been shown in vitro to be often caused by ATP-binding cassette (ABC) transporters. These transporters are frequently overexpressed in human cancers and confer an adverse prognosis in many common malignancies. The genetic factors, however, that initiate their expression in cancer are largely unknown. Here we report that the major multidrug transporter ABCG2 (BCRP/MXR) is directly and specifically activated by the transcription factor E2F1—a factor perturbed in the majority of human cancers. E2F1 regulates ABCG2 expression in multiple cell systems, and, importantly, we have identified a significant correlation between elevated E2F1 and ABCG2 expression in human lung cancers. We show that E2F1 causes chemotherapeutic drug efflux both in vitro and in vivo via ABCG2. Furthermore, the E2F1–ABCG2 axis suppresses chemotherapy-induced cell death that can be restored by the inhibition of ABCG2. These findings therefore identify a new axis in multidrug resistance and highlight a radical new function of E2F1 that is relevant to tumor therapy.
LanguageEnglish
Pages4164-4172
Number of pages9
JournalOncogene
Volume33
Early online date25 Nov 2013
DOIs
StatePublished - 2014

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Drug Resistance
Multiple Drug Resistance
Neoplasms
E2F1 Transcription Factor
Drug Therapy
ATP-Binding Cassette Transporters
Lung Neoplasms
Cell Death
Pharmaceutical Preparations
In Vitro Techniques
Therapeutics

Keywords

  • E2F1
  • ABCG2
  • drug sensitivity
  • multidrug transporters
  • cancer

Cite this

Rosenfeldt, M., Bell, L., Long, J., O'Prey, J., Nixon, C., Roberts, F., ... Ryan, K. (2014). E2F1 drives chemotherapeutic drug resistance via ABCG2. Oncogene, 33, 4164-4172. DOI: 10.1038/onc.2013.470
Rosenfeldt, Mathias ; Bell, Laura ; Long, Jaclyn ; O'Prey, Jim ; Nixon, Colin ; Roberts, Fiona ; Dufès, Christine ; Ryan, Kevin. / E2F1 drives chemotherapeutic drug resistance via ABCG2. In: Oncogene. 2014 ; Vol. 33. pp. 4164-4172
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Rosenfeldt, M, Bell, L, Long, J, O'Prey, J, Nixon, C, Roberts, F, Dufès, C & Ryan, K 2014, 'E2F1 drives chemotherapeutic drug resistance via ABCG2' Oncogene, vol. 33, pp. 4164-4172. DOI: 10.1038/onc.2013.470

E2F1 drives chemotherapeutic drug resistance via ABCG2. / Rosenfeldt, Mathias; Bell, Laura; Long, Jaclyn; O'Prey, Jim; Nixon, Colin; Roberts, Fiona; Dufès, Christine; Ryan, Kevin.

In: Oncogene, Vol. 33, 2014, p. 4164-4172.

Research output: Contribution to journalArticle

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AU - Rosenfeldt,Mathias

AU - Bell,Laura

AU - Long,Jaclyn

AU - O'Prey,Jim

AU - Nixon,Colin

AU - Roberts,Fiona

AU - Dufès,Christine

AU - Ryan,Kevin

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Rosenfeldt M, Bell L, Long J, O'Prey J, Nixon C, Roberts F et al. E2F1 drives chemotherapeutic drug resistance via ABCG2. Oncogene. 2014;33:4164-4172. Available from, DOI: 10.1038/onc.2013.470