Abstract : The goal of this project is to identify members of the MDC protein family that are expressed in breast cancer tissue, to develop novel antibodies to them, and to determine their distribution in tumor tissue as well as in cultured breast cancer cell lines. As a model system for breast cancer progression, we are using transgenic mice that express the polyomavirus middle T oncogene in the mammary gland epithelium. Using the polymerase chain reaction (PCR), we have shown that MDC9 and MDC15 are expressed in mammary tumor tissue derived from these mice. We have raised polyclonal antibodies to synthetic peptides and recombinant proteins, but these antibodies did not recognize the cognate antigens in mammary tumor tissue, presumably due to lack of cross-reaction with the native proteins. We have also raised panels of rabbit monoclonal antibodies to proteins expressed on the surface of mammary tumor cells, and have identified several of the corresponding antigens. We are continuing to screen these antibodies for reactivity with MDCs. In addition, we are using DNA immunization as a direct approach to raising anti-MDC monoclonal antibodies.