Multiplex profiling identifies clinically relevant signalling proteins in an isogenic prostate cancer model of radioresistance

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作者
S. Inder
M. Bates
N. Ni Labhrai
N. McDermott
J. Schneider
G. Erdmann
T. Jamerson
V. A. Belle
A. Prina-Mello
P. Thirion
P. R. Manecksha
D. Cormican
S. Finn
T. Lynch
L. Marignol
机构
[1] Translational Radiobiology and Molecular oncology,Department of Urology
[2] Applied Radiation Therapy Trinity,Department of International Health
[3] Trinity Translational Medicine Institute (TTMI),Department of Clinical Medicine
[4] Trinity College Dublin,Department of Surgery
[5] St James’s Hospital,Department of Histopathology
[6] NMI TT Pharmaservices,undefined
[7] Mount Sinai School of Medicine,undefined
[8] Laboratory for Biological Characterization of Advanced Materials (LBCAM),undefined
[9] Trinity Translational Medicine Institute (TTMI),undefined
[10] AMBER centre at CRANN Institute,undefined
[11] Trinity College Dublin,undefined
[12] School of Medicine,undefined
[13] Trinity College Dublin,undefined
[14] St Luke’s Radiation Oncology Network,undefined
[15] St James’s Hospital,undefined
[16] Trinity College Dublin,undefined
[17] St James’s Hospital,undefined
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摘要
The exact biological mechanism governing the radioresistant phenotype of prostate tumours at a high risk of recurrence despite the delivery of advanced radiotherapy protocols remains unclear. This study analysed the protein expression profiles of a previously generated isogenic 22Rv1 prostate cancer model of radioresistance using DigiWest multiplex protein profiling for a selection of 90 signalling proteins. Comparative analysis of the profiles identified a substantial change in the expression of 43 proteins. Differential PARP-1, AR, p53, Notch-3 and YB-1 protein levels were independently validated using Western Blotting. Pharmacological targeting of these proteins was associated with a mild but significant radiosensitisation effect at 4Gy. This study supports the clinical relevance of isogenic in vitro models of radioresistance and clarifies the molecular radiation response of prostate cancer cells.
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