Characterization of an Adhesion Associated Tumor Suppressor in Breast Cancer
Annual rept. 1 Aug 1998-31 Jul 1999
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We identified the D7 antigen in a screen for kinases that are overexpressed in Ras-transformed breast epithelia. We generated monoclonal antibodies specific for tyrosine phosphorylated proteins in breast cancer cells and focussed upon one particular antigen that was overexpressed in transformed epithelia. We also linked the function of D7 with the E-cadherin tumor suppressor. Our first objective was to identify the D7 antigen, determine the basis of its enzymatic activity as a tyrosine or serinethreonine kinase, and determine if D7 interacts with E-cadherin. Our second objective was to measure the phosphorylation and enzymatic activity of this kinase in normal and transformed epithelia. Our final objective was to measure D7 expression in breast cancer cells and determine if D7 EphA2 overexpression altered cell growth, migration or invasiveness. In this progress report, we demonstrate that the D7 antigen is the EphA2 receptor tyrosine kinase. We find that E-cadherin stabilizes the binding of EphA2 to its cell-bound ligands. We also demonstrate gross overexpression of EphA2 in malignant breast cancer cells as confirmed both with cellular models and in archival specimens of breast cancer tissues. Altogether, our results demonstrate extraordinary potential of EphA2 as a marker and target of malignant breast cancer.
- Medicine and Medical Research