Breast cancer is a molecularly heterogeneous disease, and predicting response to
chemotherapy remains a major clinical challenge. To minimize adverse side-effects or cumulative toxicity in patients unlikely to benefit from treatment,
biomarkers indicating treatment efficacy are critically needed. iTRAQ labeling coupled with multidimensional LC-MS/MS of the enriched mitochondria and endoplasmic reticulum fraction, key organelles regulating apoptosis, has led to the discovery of several differentially abundant
proteins in
breast cancer cells treated with the chemotherapeutic agent
doxorubicin followed by the
death receptor ligand, TRAIL, among 571 and 801 unique
proteins identified in ZR-75-1 and MDA-MB-231
breast cancer cell lines, respectively. The differentially abundant
proteins represent diverse biological processes associated with cellular assembly and organization, molecular transport, oxidative stress, cell motility, cell death, and
cancer. Despite many differences in molecular phenotype between the two
breast cancer cell lines, a comparison of their subproteomes following
drug treatment revealed three
proteins displaying common regulation: PPIB, AHNAK, and SLC1A5. Changes in these
proteins, detected by iTRAQ, were confirmed by immunofluorescence, visualized by confocal microscopy. These novel potential
biomarkers may have clinical utility for assessing response to
cancer treatment and may provide insight into new therapeutic targets for
breast cancer.