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 (HSPs) in two pairs of matched parental/radioresistant
breast cancer cell lines. We were able to quantify 43 and 42 HSPs
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 the HSP70 and HSP40 subfamilies of HSPs exhibited 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.