Detection of protein alterations in male breast cancer using two dimensional gel electrophoresis and mass spectrometry: The involvement of several pathways in tumorigenesis

Background: Little emphasis has been placed today on the elucidation of protein alterations in male breast carcinogenesis. Methods: Protein extracts were subjected to both isoelectric focusing (IEF) and non-equilibrium pH gradient electrophoretic (NEPHGE) analyses. Differentially expressed proteins in tumor tissues were identified by matrix assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry and database search. Results: Some of the alterations involve variations in the expression of cytokeratins 8, 18 and 19. More interestingly, tropomyosinl, a protein known to play a role in suppression of the malignant phenotype, was found to be under-expressed in cancer tissues, implicating a possible pivotal role for this protein in male breast carcinogenesis. Co-upregulation of molecular chaperones (heat shock protein HSP27 and protein disulfide isomerase), stress related proteins (peroxiredoxin 1 and peptidylprolyl isomerase A) and glycolytic enzymes (enolase 1) occurred also in male breast tumors. Some of the remaining alterations include proteins involved in invasion and metastasis, such as galectin 1 and cathepsin D. Conclusions: The present study represents a first proteomic investigation of protein alterations in infiltrating ductal carcinomas (IDCA) of the male breast. A number of protein alterations in tumor tissues have been characterised thus, providing new insights into the molecular mechanisms underlying this disease. (c) 2007 Elsevier B.V All rights reserved.