Targeted Profiling of Heat Shock Proteome in Radioresistant Breast Cancer Cells.

Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer death in women. Radioresistance remains one of the most critical barriers in radiation therapy for breast cancer. In this study, we employed a parallel-reaction monitoring (PRM)-based targeted proteomic method to examine the reprogramming of the heat shock proteome during the development of radioresistance in breast cancer. In particular, we investigated the differential expression of heat shock proteins in two pairs of matched parental/radioresistant breast cancer cell lines. We were able to quantify 43 and 42 heat shock proteins in the MCF-7 and MDA-MB-231 pairs of cell lines, respectively. By analyzing the commonly altered proteins, we found that several members of HSP70 and HSP40 subfamilies of heat shock proteins were with substantially altered expression upon development of radioresistance. Moreover, the expression of HSPB8 is markedly elevated in the radioresistant lines relative to the parental MCF-7 and MDA-MB-231 cells. Together, our PRM-based targeted proteomics method revealed the reprogramming of the heat shock proteome during the development of radioresistance in breast cancer cells and offered potential targets for sensitizing breast cancer cells toward radiation therapy.