Proteomic and PROTEOMEX profiling of mammary cancer progression in a HER-2/neu oncogene-driven animal model system.

Abstract

The prevention of mammary carcinoma by immunological strategies targeting the HER-2/neu receptor has proved to be effective in preclinical models. Thus, a well-characterized HER-2/neu oncogene-driven mammary carcinogenesis model was analysed by various profiling strategies following "triplex" vaccination to identify new candidate targets for breast cancer immunoprevention. 2-DE-based proteomic profiling of preneoplastic and tumour lesions versus normal and aged mammary tissue demonstrated that tumour progression was associated with an up-regulation of molecular chaperones including glucose-regulated protein (GRP)78 and of proteins favouring cell motility, which was in line with the corresponding transcriptomic profiling data. Furthermore, PROTEOMEX analyses suggested that naturally induced autoantibody responses occur during early phases of mammary cancer progression. Most of the cancer progression-induced antibodies targeted proteins of normal and preneoplastic mammary glands. However, three proteins were only recognized by sera obtained from vaccinated mice, including 2 isoforms of annexin A6. The distinct expression patterns for annexin A6 and GRP78 during tumour progression were further verified by western blot and/or immunoprecipitation. In addition, an inhibitor-mediated blockade of GRP78 expression in a model cell line caused a reduced cell growth. Thus, the proteome-based approaches applied in the murine BALB-NeuT model might indeed provide candidates for immunoprevention strategies in breast cancer.

• Authors: Stefania Croci, Christian V Recktenwald, Rudolf Lichtenfels, Giordano Nicoletti, Sven P Dressler, Carla De Giovanni, Annalisa Astolfi, Arianna Palladini, Kazuo Shin-ya, Lorena Landuzzi, Patrizia Nanni, Pier-Luigi Lollini, Barbara Seliger
• Journal: Proteomics (Proteomics) Vol. 10 Issue 21 Pg. 3835-53 (Nov 2010) ISSN: 1615-9861 [Electronic] Germany
• PMID: 20957756 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Neoplasm
• Autoantibodies
• Cancer Vaccines
• Endoplasmic Reticulum Chaperone BiP
• Heat-Shock Proteins
• Hspa5 protein, mouse
• Immunoglobulin G
• Receptor, ErbB-2

Topics

• Animals
• Antibodies, Neoplasm (blood)
• Autoantibodies (blood)
• Cancer Vaccines (pharmacology)
• Cell Line, Tumor
• Cluster Analysis
• Disease Models, Animal
• Disease Progression
• Electrophoresis, Gel, Two-Dimensional
• Endoplasmic Reticulum Chaperone BiP
• Female
• Gene Expression Profiling
• Heat-Shock Proteins (genetics, metabolism)
• Immunoblotting
• Immunoglobulin G (blood)
• Mammary Neoplasms, Experimental (immunology, metabolism, pathology, therapy)
• Mice
• Mice, Inbred BALB C
• Mice, Transgenic
• Principal Component Analysis
• Proteomics (methods)
• Receptor, ErbB-2 (biosynthesis, genetics, metabolism)
• Reproducibility of Results