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Proteomic identification of putative biomarkers of radiotherapy resistance: a possible role for the 26S proteasome?

Smith, Laura; Qutob, Omar; Watson, Mark B.; Beavis, Andrew W.; Potts, Donna; Welham, Kevin J.; Garimella, Veerabhadram; Lind, Michael J.; Drew, Philip J.; Cawkwell, Lynn

Authors

Laura Smith

Omar Qutob

Mark B. Watson

Andrew W. Beavis

Donna Potts

Kevin J. Welham K.J.Welham@hull.ac.uk

Veerabhadram Garimella

Professor Michael Lind M.J.Lind@hull.ac.uk
Foundation Professor of Oncology/ Head of the Joint Centre for Cancer Studies

Philip J. Drew



Abstract

PURPOSE: We aimed to identify putative predictive protein biomarkers of radioresistance. EXPERIMENTAL DESIGN: Three breast cancer cell lines (MCF7, MDA-MB-231, and T47D) were used as in vitro models to study radioresistance. Inherent radiosensitivities were examined using a clonogenic survival assay. It was revealed that each cell line differed in their response to radiotherapy. These parental breast cancer cell lines were used to establish novel derivatives (MCF7RR, MDA-MB-231RR, and T47DRR) displaying significant resistance to ionizing radiation. Derivative cells were compared with parental cells to identify putative biomarkers associated with the radioresistant phenotype. To identify these biomarkers, complementary proteomic screening approaches were exploited encompassing two-dimensional gel electrophoresis in combination with mass spectrometry, liquid chromatography coupled with tandem mass spectrometry and quantitative proteomics using iTRAQ technology. RESULTS: A large number of potential biomarkers were identified, and several of these were confirmed using Western blot analysis. In particular, a decrease in the expression of the 26S proteasome was found in all radioresistant derivatives when compared with the respective parent cells. Decreased expression of this target was also found to be associated with radioresistant laryngeal tumors (P=.05) in a small pilot immunohistochemical study. CONCLUSIONS: These findings suggest that the 26S proteasome may provide a general predictive biomarker for radiotherapy outcome.

Journal Article Type Article
Publication Date 2009-11
Journal NEOPLASIA
Print ISSN 1522-8002
Electronic ISSN 1476-5586
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 11
Issue 11
Pages 1194-1207
APA6 Citation Smith, L., Qutob, O., Watson, M. B., Beavis, A. W., Potts, D., Welham, K. J., …Cawkwell, L. (2009). Proteomic identification of putative biomarkers of radiotherapy resistance: a possible role for the 26S proteasome?. Neoplasia, 11(11), (1194-1207). doi:10.1593/neo.09902. ISSN 1522-8002
DOI https://doi.org/10.1593/neo.09902
Keywords Cancer Research
Copyright Statement Attribution-NonCommercial-NoDerivs 3.0 Unported (CC BY-NC-ND 3.0)

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Copyright Statement
Attribution-NonCommercial-NoDerivs 3.0 Unported (CC BY-NC-ND 3.0)





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