Multiplex profiling identifies clinically relevant signalling proteins in an isogenic prostate cancer model of radioresistance.
Biomarkers, Tumor
/ metabolism
Cell Line, Tumor
Cell Survival
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Humans
Male
Models, Biological
Poly (ADP-Ribose) Polymerase-1
/ metabolism
Prostatic Neoplasms
/ drug therapy
Protein Array Analysis
/ methods
Radiation Tolerance
Receptor, Notch3
/ metabolism
Receptors, Androgen
/ metabolism
Tumor Suppressor Protein p53
/ metabolism
Y-Box-Binding Protein 1
/ metabolism
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
22 11 2019
22 11 2019
Historique:
received:
25
05
2018
accepted:
04
11
2019
entrez:
24
11
2019
pubmed:
24
11
2019
medline:
4
11
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31758038
doi: 10.1038/s41598-019-53799-7
pii: 10.1038/s41598-019-53799-7
pmc: PMC6874565
doi:
Substances chimiques
AR protein, human
0
Biomarkers, Tumor
0
NOTCH3 protein, human
0
Receptor, Notch3
0
Receptors, Androgen
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Y-Box-Binding Protein 1
0
YBX1 protein, human
0
PARP1 protein, human
EC 2.4.2.30
Poly (ADP-Ribose) Polymerase-1
EC 2.4.2.30
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
17325Subventions
Organisme : NIMHD NIH HHS
ID : T37 MD001452
Pays : United States
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