Journal
JOURNAL OF PROTEOME RESEARCH
Volume 20, Issue 5, Pages 2830-2838Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.1c00075
Keywords
quantitative proteomics; parallel-reaction monitoring; SILAC; kinase; kinome; breast cancer; radioresistance; TAF9
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Funding
- National Institutes of Health [R01 CA210072]
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The study utilized SILAC and PRM methods to investigate the differential expression of kinases in breast cancer cells, revealing that the differentially expressed kinase TAF9 enhances radioresistance in breast cancer cells and plays a role in upregulating genes associated with radioresistance.
Radiotherapy constitutes a major therapeutic modality for early management of breast cancer. Despite the high efficacy in treating breast cancer (BC), radiation resistance and tumor recurrence are major hurdles in breast cancer radiotherapy. Herein, stable isotope labeling by amino acids in cell culture (SILAC) was employed, along with the parallel-reaction monitoring (PRM)-based targeted quantitative proteomic method, to examine the differences in kinase protein expression in MCF-7 and MDA-MB-231 breast cancer cells and their corresponding radioresistant C6 and C5 clones. We quantified the relative protein expression levels of 300 and 281 kinases in C5/MDA-MB-231 and C6/MCF-7 pairs of breast cancer cells, respectively. We also showed that TAF9, which was one of the differentially expressed kinases, enhances radiation resistance in breast cancer cells. Moreover, a correlation analysis of gene expression suggested TAF9's role in upregulating the expression of genes involved with radioresistance. Overall, our study uncovered a large number of differentially expressed kinases accompanied with the acquisition of radioresistance and revealed a role of TAF9 in promoting radioresistance in breast cancer.
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