title: Proteome changes induced by overexpression of the p75 neurotrophin receptor (p75NTR) in breast cancer cells.
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.
authors.affiliation: INSERM U 908 Growth factor signaling in breast cancer cells. Functional proteomics, IFR-147, University of Lille, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Wilmet
authors.forename: Christophe
authors.initials: C
authors.lastname: Tastet
authors.forename: Emilie
authors.initials: E
authors.lastname: Desruelles
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ziental-Gelus
authors.forename: Vincent
authors.initials: V
authors.lastname: Blanckaert
authors.forename: Hubert
authors.initials: H
authors.lastname: Hondermarck
authors.forename: Xuefen
authors.initials: X
authors.lastname: Le Bourhis
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology; D053719:Tandem Mass Spectrometry
chemical_list: C484065:NGFR protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D020543:Proteome; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017475:Receptors, Nerve Growth Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human