New approaches to proteomic analysis of breast cancer

Proteomic based approaches are beginning to be utilized to study the natura l history and treatment of breast cancer. A variety of proteomics approache s are under study, and are summarized herein. Two-dimensional gel electroph oresis (2D-PAGE) is still the foundation of most proteomics studies. We pre sent an analysis of 2D-PAGE studies reported to date in breast cancer, incl uding those examining normal/tumor differences and selected populations of breast cells. Newer technologies such as laser capture microdissection and highly sensitive mass spectrometry methods are currently being used togethe r to identify greater numbers of lower abundance proteins that are differen tially expressed between defined cell populations. Novel technologies still in developmental phases will enable identification of validated targets in small biopsy specimens, including high density protein arrays, antibody ar rays and lysate arrays. Surface-enhanced laser desorption/ionization time-o f-flight (SELDI-TOF) analysis enables the high throughput characterization of lysates from very few tumor cells and may be best suited for clinical bi omarker studies. We present SELDI-TOF data herein to show the accuracy of t he method in a small cohort of breast tumors, as well as its potential disc riminatory capability. Such technologies are expected to supplement our arm amentarium of mRNA-based assays, and provide critical information on protei n levels and post-translational modifications.