Differential phosphopeptide expression in a benign breast tissue, and triple-negative primary and metastatic breast cancer tissues from the same African-American woman by LC-LTQ/FT-ICR mass spectrometry

Abstract African-American women have a higher risk for developing triple-negative breast cancer (TNBC). Lacking the expression of receptors for estrogen and progesterone, and without human epidermal growth factor 2 receptor gene amplification, TNBC is a very aggressive type of breast cancer with a high likelihood of metastasis and recurrence. Specific therapeutic targets for this aggressive disease remain to be identified. Phosphorylation, a post-translational modification that adds one or more phosphate groups to a protein, plays a key role in the activation and deactivation of a protein’s cellular function. Here, we report the first systematic phosphoproteomic analysis of a benign breast tissue, a primary breast cancer tissue, and a metastatic breast cancer tissue from the same African-American woman. Differential phosphoprotein levels were measured with reversed-phase nano-liquid chromatography coupled to a hybrid linear quadrupole ion trap/Fourier transform ion cyclotron resonance mass spectrometer (LC-LTQ/FT-ICR MS). Five proteins were found to be highly phosphorylated in the metastatic site whereas six proteins were highly phosphorylated in the cancer site of the TNBC patient. Identified phosphoproteins are known to be involved in breast cancer signal transduction pathways and these results may identify new diagnostic and therapeutic targets for TNBC.