Int. J. Dev. Biol. 55: 801 - 809 (2011)

https://doi.org/10.1387/ijdb.113345jw

Vol 55, Issue 7-8-9

Special Issue: Mammary Gland in Development & Cancer

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

Published: 29 November 2011

Jean-Philippe Wilmet¹, Christophe Tastet¹, Emilie Desruelles¹, Nathalie Ziental-Gelus¹, Vincent Blanckaert², Hubert Hondermarck*^,1 and Xuefen Le Bourhis¹

SUP>1INSERM U 908 "Growth factor signaling in breast cancer cells. Functional proteomics", IFR-147, University of Lille and ²EA-2160 MMS, University of Maine, France.

Abstract

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.

Keywords

breast cancer, neurotrophin receptor p75^NTR, TRAIL, proteomics