In human breast cancer, c‐Src activity is elevated compared to normal breast tissue. It is not yet known whether this increase in c‐Src activity is accompanied by an increase in c‐Src protein expression. In this study, c‐Src activity and protein expression were determined in a series of human breast cancers and in normal breast tissue, using immune complex kinase assays and immunoblotting. As the heterogeneity of breast cancer is not taken into account in these biochemical experiments, immunohistochemistry was also used to distinguish between normal and malignant cells. In human breast cancers, the c‐Src activity is increased 4‐ to 30‐fold, compared with normal breast tissue. This enhanced activity is accompanied by an increase in c‐Src protein expression, as shown by both immunoblotting and immunohistochemistry. Immunohistochemistry indicates that the majority of c‐Src appears to be concentrated around the nucleus in malignant cells, whereas in normal cells, it is distributed more evenly in the cytoplasm. These data confirm that c‐Src activity is increased in human breast cancer. In addition, this study provides strong immunohistochemical evidence that the c‐Src protein is also overexpressed, enabling a distinction to be made between normal and malignant cells.

Overexpression of EGFR and c-erbB2 frequently occurs in human breast cancers, correlating with poor prognosis. Here we show that overexpression of EGFR and c-erbB2 in cell lines increases cell migration, an important step in metastasis formation. The effect of EGFR on migration is dependent on the addition of EGF to the cells. In contrast, c-erbB2 seems to act independently of its ligand in these assays. Overexpression of this receptor is sufficient to induce cell migration. In addition, we investigated the involvement of a number of signal transduction pathways known to be activated by the EGFR. We found that inactivation of MAPKK results in a decreased migration, while inactivation of PI3K increases migration.z 1998 Federation of European Biochemical Societies.

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