Proteome changes induced by overexpression of the neurotrophin receptor p75 neurotrophin receptor (p75~(NTR)) in breast cancer cells

摘要

In breast cancer cells, the neurotrophin receptor p75~(NTR) acts as a prosurvival factor able to stimulate resistance to apoptosis, but its mechanism of action remains incompletely defined. In this study, we investigated the global proteome modification induced by p75~(NTR) overexpression in breast cancer cells treated by the pro-apoptotic agent tumor necrosis factor (TNF)-related-apoptosis- inducing-ligand (TRAIL). p75~(NTR) was stably overexpressed in the MCF-7 breast cancer cells and the impact of a treatment by TRAIL was investigated in wild type vs. p75~(NTR) overexpressing cells. Proteins were separated in two-dimensional electrophoresis, and regulated spots were detected by computer assisted analysis before identification by MALDI-TOF/TOF mass spectrometry. In the absence of TRAIL treatment, p75~(NTR) did not induce any change in the proteome of breast cancer cells. In contrast, after treatment with TRAIL, fragments of cytokeratin-8, -18 and -19, as well as full length cytokeratin-18, were up-regulated by p75~(NTR) overexpression. Of note, spectrin alpha-chain and the ribosomal protein RPLP0 were induced by TRAIL, independently of p75~(NTR) level. Interestingly, the well known stress-induced protein HSP-27 was less abundant when p75~(NTR) was overexpressed, indicating that p75~(NTR) overexpression reduced TRAIL induced cell stress. These data indicate that overexpression of p75~(NTR) induces proteome modifications in breast cancer cells and provide information on how this receptor contributes in tumor cell resistance to apoptosis.