Endocrine Abstracts (2016) 42 P34 | DOI: 10.1530/endoabs.42.P34

Mechanisms of radioresistance in prostate cells

Fabian Guggenberger1, Holger Erb2, Ira-Ida Skvortsova3, Zoran Culig1 & Frédéric R. Santer1

1Division of Experimental Urology, Medical University of Innsbruck, Innsbruck, Austria; 2YCR Cancer Research Unit, Department of Biology, University of York, York, UK; 3Department of Therapeutic Radiology and Oncology, Medical University of Innsbruck, Innsbruck, Austria

Among androgen deprivation therapy (ADT), radiation therapy is an approved treatment either for early stage local PCa, but also for metastatic M1 stage PCa. However, tumour relapse is a frequent event that affects about 80% of patients undergoing prior treatment. There is increasing evidence that the occurrence of cancer stem cells (CSC) may play an important role in therapy resistance, in particular also in radioresistance. However, our knowledge on the mechanisms of radioresistance of the prostatic basal layer is still limited. The aim of this study is to identify a novel molecular mechanism underlying radioresistance in the prostate basal cell layer containing stem cells. In this study benign primary prostate basal epithelial cells (PrEPs) obtained from 5 patients were isolated and cultured in the presence of a feeder layer. The PrEPs were characterised by clonogenic assays and by label retention assay using FACS analysis subsequent to PKH67 membrane labelling, which might indicate the presence of stem cells within the cultures. The PrEPs were irradiated for 21 times following a therapeutic schedule with 0, 0.5 or 1 Gray using a linear particle accelerator (LINAC). NextGen transcriptome sequencing was performed and bioinformatical analysis, including pathway analysis, is in progress. Once it is finished a careful review of literature is performed. Based thereon a candidate gene, whose expression is shown to be strongly altered by irradiation, is chosen for further experiments (e.g. knock-down, over-expression, inhibition) that will test the candidate’s involvement in radioprotection. This may improve co-treatment strategies for future irradiation therapy.

Presenting Author: Fabian Guggenberger, Department of Urology, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria. Email: fabian.guggenberger@i-med.ac.at

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