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Radiation Oncology
Published in: Radiation Oncology 1/2015

Open Access 01-12-2015 | Research

The expression level of the transcription factor Aryl hydrocarbon receptor nuclear translocator (ARNT) determines cellular survival after radiation treatment

Authors: Markus Mandl, Maria- Katharina Lieberum, Juergen Dunst, Reinhard Depping

Published in: Radiation Oncology | Issue 1/2015

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Abstract

Background

Tumour hypoxia promotes radioresistance and is associated with poor prognosis. The transcription factor Aryl hydrocarbon receptor nuclear translocator (ARNT), also designated as Hypoxia-inducible factor (HIF)-1β, is part of the HIF pathway which mediates cellular adaptations to oxygen deprivation and facilitates tumour progression.
The subunits HIF-1α and ARNT are key players within this pathway. HIF-1α is regulated in an oxygen-dependent manner whereas ARNT is considered to be constitutively expressed. However, there is mounting evidence that certain tumour cells are capable to elevate ARNT in hypoxia which suggests a survival benefit.
Therefore the objective of this study was to elucidate effects of an altered ARNT expression level on the cellular response to radiation.

Methods

Different human cell lines (Hep3B, MCF-7, 786-Owt, 786-Ovhl, RCC4wt and RCC4vhl) originating from various tumour entities (Hepatocellular carcinoma, breast cancer and renal cell carcinoma respectively) were X-irradiated using a conventional linear accelerator. Knockdown of ARNT expression was achieved by transient siRNA transfection. Complementary experiments were performed by forced ARNT overexpression using appropriate plasmids. Presence/absence of ARNT protein was confirmed by Western blot analysis. Clonogenic survival assays were performed in order to determine cellular survival post irradiation. Statistical comparison of two groups was achieved by the unpaired t-test.

Results

The results of this study indicate that ARNT depletion renders tumour cells susceptible to radiation whereas overexpression of this transcription factor confers radioresistance.

Conclusions

These findings provide evidence to consider ARNT as a drug target and as a predictive marker in clinical applications concerning the response to radiation.
Appendix
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Metadata
Title
The expression level of the transcription factor Aryl hydrocarbon receptor nuclear translocator (ARNT) determines cellular survival after radiation treatment
Authors
Markus Mandl
Maria- Katharina Lieberum
Juergen Dunst
Reinhard Depping
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2015
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-015-0539-9

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