. Insights into a plasma membrane signature. Physiol Genomics 5: [129][130][131][132][133][134][135][136] 2001.-The plasma membrane (PM) is an organized biological system that serves as a structural barrier and communication interface with the extracellular environment. Many basic questions regarding the PM as a system remain unanswered. In particular, we do not understand the scope of similarity and differences in protein expression at the PM. This study takes an initial step toward addressing these questions by comparing the PM proteomes of fibroblasts and mammary carcinoma cells. Three sets of proteins were revealed by the study. The first set comprises between 9 and 23% of all proteins at the PM and appears to be common to both fibroblasts and mammary carcinoma. A second group of proteins, comprising ϳ40% of the proteins at the PM, is tightly linked to cell lineage. The third set of proteins is unique to each cell line and is independent of cell lineage. It is reasonable to hypothesize then, that this third group of proteins is responsible for unique aspects of cell behavior. In an effort to find proteins linked to the metastatic phenotype, we identified several proteins that are uniquely expressed at the PM of the metastatic MDA-MB-435 cells. These proteins have functions ranging from cell adhesion to the regulation of translation and the control of oxidant stress.proteome; expression profiling; breast cancer; metastasis AS EARLY as 1953, Nordling (19) suggested that the clinical manifestations of cancer result from the cumulative effect of multiple genetic mutations. The multifactorial nature of tumor progression precludes its explanation by any single factor or even a small group of factors. It has yet to be determined how many alterations must occur to convert a normal mammary epithelial cell to carcinoma or how many additional changes are necessary for the carcinoma to progress to invasive disease. Answers to these questions require global examinations of biological systems.This study focuses on the plasma membrane (PM) as a system. The PM regulates many aspects of tumor progression including cellular differentiation, cell proliferation, adhesion and migration, pericellular proteolysis, and even the escape from immune surveillance. Each of these events represents a point for potential therapeutic intervention, making the PM a rich source of drug targets. Many of the molecules at the PM are also exposed to the extracellular milieu, providing an additional therapeutic advantage. As recognized more than 25 years ago by Garth Nicolson, there is a great need to define the PM as a system: "It would be convenient if these (biological) properties were definable by unique cell surface characteristics which were readily identifiable so that highly specific molecular approaches to fighting cancer could be developed" (18).Presented with this long-recognized but unmet need, the present study was aimed at gaining some basic information on the PM proteome of mammary carcinoma. We compared the PM proteomes of mammary...

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