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2002 Scientific Report

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The adhesion of normal

The adhesion of normal melanocytes to the extracellular matrix induces the formation of focal adhesion complexes and actin stress fibers (Figure 3), but in a highly metastatic melanoma cell line, these structures are absent. We are exploring the biochemical basis for this difference. We have found that the activity level of Rac (a small GTPase required for regulating actin structure) is elevated and that the inhibition of PKC blocks this activity. The levels of PKCa are elevated in these cells as well. We are exploring the effects on cell structure, adhesion, and migration of PKCα levels. Figure 3. Focal adhesions (green spots) and stress fibers (red fibers) are absent in metastatic melanoma External Collaborators Joan Brugge, Harvard Medical School, Boston, Massachusetts Beatrice Knudsen, Cornell University Medical College, New York, New York Senthil Muthuswamy, Cold Spring Harbor Laboratory, New York Benjamin Neel, Beth Israel Deaconess Medical Center, Harvard Institute of Medicine, Boston, Massachusetts David Shalloway, Cornell University, Ithaca, New York Sheila Thomas, Harvard Institute of Medicine, Boston, Massachusetts Publications Miranti, Cindy K. 2002. Application of cell adhesion to study signaling networks. In Methods in Cell Matrix Adhesion, J.C. Adams, ed. Methods in Cell Biology series, San Diego: Academic Press, pp. 359–383. Miranti, Cindy K., and Joan S. Brugge. 2002. Sensing the environment: a historical perspective on integrin signal transduction. Nature Cell Biology 4(4): E83–E90. Woodside, Darren G., A. Obergfell, Lijun Leng, Julie L. Wilsbacher, Cindy K. Miranti, Joan S. Brugge, Sanford J. Shattil, and Mark H. Ginsberg. 2001. Activation of Syk protein tyrosine kinase through interaction with integrin β cytoplasmic domains. Current Biology 11(22): 1799–1804. Left to right: Pearson, Putnam, Bill, Patacsil, Miranti 35

Human breast ductal epithelium This tissue was stained with two antibodies. In red is c-Met (polyclonal antibody c28) and in green is c-neu (monoclonal antibody OCS). c-neu stains for the tyrosine kinase receptor Her2-neu (involved in cell signal processes) that is amplified in breast cancer in 10–20% of primary cases. The protein c-Met is also a tyrosine kinase receptor that is activated by the ligand hepatocyte growth factor/scatter factor (HGF/SF); c-Met has been shown to be a prognostic marker for human breast cancer. Co-localized foci are colored yellow, while red and green label the Met and her2neu separately. The c-Met is evident on the lumenal and basal border; c-neu is less specific but may be increased in the lateral boundaries between cells. (Resau) 36

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