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

Little emphasis has been placed today on the elucidation of protein alterations in male breast carcinogenesis. 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. Some of the alterations involve variations in the expression of cytokeratins 8, 18 and 19. More interestingly, tropomyosin1, 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. 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.