Targeted Proteomic Analysis Revealed Kinome Reprogramming during Acquisition of Radioresistance in Breast Cancer Cells

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.